Nitration or carboxylation catalysts

ABSTRACT

In the presence of an imide compound (e.g., N-hydroxyphthalimide) shown by the following formula (1):                    
     wherein R 1  and R 2  represent a hydrogen atom, a halogen atom, an alkyl group, an aryl group and a cycloalkyl group, and R 1  and R 2  may bond together to form a double bond, or an aromatic or non-aromatic ring, and Y is an O or OH, and n denotes 1 to 3; 
     a substrate is allowed to contact with at least one reactant selected from (i) a nitrogen oxide and (ii) a mixture of carbon monoxide and oxygen to be introduced with at least one functional group selected from a nitro group and a carboxyl group. The nitrogen oxide includes, for example, a compound represented by the formula N x O y  (e.g., N 2 O 3 , NO 2 ). The substrate includes, for example, a compound having a methine carbon atom (e.g., adamantane), a compound having a methyl group or a methylene group at an adjacent moiety of an aromatic ring. According to such reaction, the substrate can be efficiently nitrated or carboxylated even in a mild or moderate condition.

This application is the national phase under 35 U.S.C. §371 of prior PCTInternational Application No. PCT/JP98/00079 which has an Internationalfiling date of Jan. 13, 1998 which designated the United States ofAmerica, the entire contents of which are hereby incorporated byreference.

TECHNICAL FIELD

The present invention relates to a catalyst useful for directly andefficiently nitrating and/or carboxylating a substrate by using at leastone reactant selected from (i) a nitrogen oxide and (ii) a mixture ofcarbon monoxide and oxygen, and a compound obtained by using thecatalyst and a process for producing the compound (anitration/carboxylation process, a process for producing a compoundhaving a nitro group and/or carboxyl group, a novel adamantanederivative, and a process for producing an adamantane derivative) usingthe catalyst.

BACKGROUND ART

Nitro compounds are commonly utilized as a raw material for medicine,agricultural chemicals, dyes, solvents and explosives, a raw materialfor amino compounds, and the like. Moreover, carboxylic acids (carboxycompounds) are useful as a raw material of a variety of compounds suchas esters. Among them, dicarboxylic acids are useful as a raw materialof polyesters.

Nitration of hydrocarbons is generally conducted by a nitric acidprocess which employs a mixed acid (a mixture of nitric acid andsulfuric acid). However, the nitric acid process requires a strong acidwith high concentration in a large amount. Besides, since the nitrationreaction is exothermic, it is difficult to improve its reactionoperability. Furthermore, in the nitric acid process, large amounts ofnitrogen oxides produce, which cause environmental pollution and thushave to be treated in a proper manner.

As a nitration process, use of N₂O₅ and ozone in the presence of an ironcatalyst has been suggested for nitration of aromatic compounds (e.g.,toluene) or alicyclic compounds (e.g., adamantane). Due to the use ofNO₃ as a reactant, this nitration process can proceed smoothly at alower temperature. However, a catalyst should be incorporated in orderto increase the reaction rate, and additional equipment such as anozone-generating apparatus should be installed for the generation ofozone.

Carboxyl compounds (e.g., phthalic acid) can be obtained by, forexample, an oxidation of a substrate (e.g., naphthalene). In Suchoxidation reaction, a carboxyl compound having carbon atoms fewer than asubstrate can be usually obtained. Moreover, in order to obtain acarboxyl compound of a bridged cyclic hydrocarbon (e.g.,1-carboxyladamantane) by an oxidation reaction, it is required that agroup which can be converted to a carboxyl group by oxidation (e.g.,methylol group) is introduced to a methine carbon atom, and then themethine carbon atom is oxidized. It is considerably difficult.

As a carboxylation process of a hydrocarbon compound, for example, aprocess for providing a carboxylic acid by using Grignard reaction isbroadly known. In this process, many reaction steps are required since asubstrate can not be directly carboxylated and include that a specialcompound such as an organic metal compound (e.g., a Grignard compound)is previously prepared from a substrate, carbon dioxide is allowed toact on the organic metal compound, and the organic metal compound ishydrolyzed to be carboxylated. Further, it is difficult to prepare theorganic metal compound, additionally the compound is not convenient tohandle.

Japanese Patent Application Laid-open No.38909/1996 (JP-A-8-38909)discloses a process which comprises contacting a substrate with oxygento oxidize in the presence of an imide compound such asN-hydroxyphthalimide to provide a corresponding oxide (e.g., acarboxylic acid). In this process, a process for producing adipic acidfrom cyclohexane is described. In this process, a carboxyl compoundhaving the same number of carbon atoms as a substrate can be obtainedusually.

On the other hand, adamantane has a three-dimensionally symmetricstructure and skeletons which insure mutual stabilization of each ring,and as a result, endowed with distinctive functions. Various highlyfunctionalized copolymers can be obtained, for example, by introducing afunctional group such as a carboxyl group or an amino group toadamantane and optionally deriving to other derivatives thereof. Therehave been proposed various production processes for obtaining suchcopolymers from a functional group-introduced adamantane derivative. Theprocesses include, for example, a process of producing a polyester[e.g., Japanese Patent Application Laid-open No. 21090/1975(JP-A-50-21090)], a process of producing a polycarbonate [e.g., U.S.Pat. No. 3,594,427], a process for producing a polyamide or a polyimide[e.g., U.S. Pat. No. 3,832,332], a process for producing a polyurethane[e.g., Japanese Patent Publication No. 12891/1969 (JP-B-44-12891)], aprocess for producing a polysulfone and a polysulfonate [e.g., U.S. Pat.No. 3,753,950], and a process for producing a vinyl polymer [e.g.,Japanese Patent Publication No. 28419/1971 (JP-B-46-28419)].

These polymers provided from an adamantane derivative have generallyexcellent functions or characteristics (high functionality). They have,for example, optical characteristics such as small light-inducing loss,high refractive index, double refraction index, excellentcharacteristics such as moisture resistance, excellent heat resistance(heat resisting property) and thermal expansivity. Such excellentcharacteristics cannot be achieved with the use of conventionalpolymers. Accordingly, applications of said polymer have beeninvestigated for optical materials such as optical fibers, opticalelements, optical lenses, hologram, optical discs, and contact lenses,transparent resin coating compositions for organic glasses, electricconductive polymers, photosensitive materials, fluorescent materials andso forth.

On the other hand, an amino derivative derived from an alcohol of anadamantane is useful for introducing various pharmaceuticals and/oragricultural chemicals each having excellent pharmacological activity,and is used as a therapeutic agent for Parkinson's disease such as“SYMMETREL” (a trade name). A diamino body of adamantane is useful as anintermediate material for antibacterial drugs (agents) or antiviraldrugs (agents).

The above mentioned diamino body (diamino form) of the adamantane isproduced by aminating a dihalo body obtained by halogenating a diol bodyof an adamantane. However, in a process for the formation of a salt ofthe diamino body obtained by aminating the dihalo body of adamantane, aside reaction tends to occur, additionally it is difficult to separateand collect a free diamino body in a high yield.

It is, therefore, an object of the present invention to provide acatalyst which can efficiently nitrate and/or carboxylate a substrate,and a nitration and/or carboxylation process using the catalyst.

It is another object of the present invention to provide a catalystwhich can nitrate or carboxylate a substrate by using at least onereactant selected from (i) a nitrogen oxide and (ii) a mixture of carbonmonoxide and oxygen even in a mild or moderate condition, and anitration and/or carboxylation process of a substrate using thecatalyst.

A further object of the present invention is to provide a catalyst whichcan provide a compound having at least one functional group selectedfrom nitro group and carboxyl group with high conversion andselectivity, and a process for producing the compound having afunctional group by using the catalyst.

Another object of the present invention is to provide a process fornitration which can utilize effectively nitrogen oxides, which causeenvironmental pollution, for providing nitro compounds with highconversion and selectivity.

Further object of the present invention is to provide a process forproducing a carboxyl compound which has more carbon atoms than thenumber of carbon atoms of a substrate, efficiently with simple operationat fewer steps.

Still further object of the present invention is to provide a noveladamantane derivative.

Still another object of the present invention is to provide a processwhich can produce a diamino body of adamantane in high yield.

DISCLOSURE OF INVENTION

The inventors of the present invention did intensive investigation toaccomplish the above objects, and finally found that a reaction of atleast one reactant selected from (i) a nitrogen oxide (e.g., N₂O₃, N₂O)and (ii) a mixture of carbon monoxide and oxygen with a substrate in thepresence of a catalyst comprising a specific imide compound, efficientlyintroduce at least one functional group selected from a nitro group anda carboxyl group to the substrate and that useful adamantane derivativesincluding a novel adamantane derivative can be produced by using theabove method.

Thus, a catalyst of the present invention is for introducing at leastone functional group selected from a nitro group or a carboxyl group toa substrate by contacting the substrate with at least one reactantselected from (i) a nitrogen oxide and (ii) a mixture of carbon monoxideand oxygen to and comprises an imide compound shown by the followingformula (1):

wherein R¹ and R² may be the same or different from each other, andrepresent a hydrogen atom, a halogen atom, an alkyl group, an arylgroup, a cycloalkyl group, a hydroxyl group, an alkoxy group, a carboxylgroup, an alkoxycarbonyl group, and an acyl group, and R¹ and R² maybond together to form a double bond, or an aromatic or non-aromaticring; Y represents an oxygen atom or a hydroxyl group; and n denotes aninteger of 1 to 3.

The catalyst may comprise the imide compound shown by the formula (1)and a co-catalyst. As the co-catalyst, there may be employed, forexample, a compound containing at least one element selected from thegroup consisting of Group 2A elements of the Periodic Table of Elements,transition metal elements and Group 3B elements of the Periodic Table ofElements.

According to the process of the present invention, in the presence ofthe imide compound shown by the formula (1), or the imide compound andthe co-catalyst, a substrate is allowed to contact with at least onereactant selected from (i) a nitrogen oxide and (ii) a mixture of carbonmonoxide and oxygen to introduce at least one functional group selectedfrom a nitro group and a carboxyl group to the substrate. The substrateincludes, for example, (a) a compound having a methyl group or amethylene group at an adjacent site of an unsaturated bond, (b) a homo-or hetero cyclic compound having a methylene group, (c) a compoundhaving a methine carbon atom, (d) a compound having a methyl group or amethylene group at an adjacent site of an aromatic ring and (e). acompound having a methylene group at an adjacent site of a carbonylgroup. As the nitrogen oxide, there may be employed, for example, acompound shown by the formula:

N_(x)O_(y)

wherein x denotes an integer of 1 or 2 and y denotes an integer of 1 to6;

such as N₂O₃, NO₂.

The present invention comprises a process for producing a compoundhaving at least one functional group selected from a nitro group and acarboxyl group by using the above process, as well.

A novel adamantane derivative of the present invention is a compoundshown by the following formula (2) or (3):

wherein X¹ represents a nitro group, an amino group or N-substitutedamino group which may be protected by a protective group, a carboxylgroup which may be protected by a protective group, or a hydroxymethylgroup which may be protected by a protective group; and X³ and X⁴ may bethe same or different from each other, and represents a hydrogen atom,an alkyl group, a nitro group, an amino group or N-substituted aminogroup which may be protected by a protective group, a carboxyl groupwhich may be protected by a protective group, a hydroxymethyl groupwhich may be protected by a protective group or an isocyanato group;

(i) when X¹ is a nitro group, X² represents an amino group or N-aminogroup which may be protected by a protective group, a hydroxymethylgroup which may be protected by a protective group, or an isocyanatogroup;

(ii) when X¹ is an amino group or N-substituted amino group which may beprotected by a protective group, X² represents an isocyanato group;

(iii) when X¹ is a carboxyl group which may be protected by a protectivegroup, X represents a hydroxymethyl group which may be protected by aprotective group, or an isocyanato group; and

(iv) when X¹ is a hydroxymethyl group which may be protected by aprotective group, X represents an isocyanato group;

wherein X⁵ represents a carbamoyl group which may have a substituent, anitro group, a substituted hydoroxycarbonylamino group, or a saturatedaliphatic acylamino group or an aromatic acylamino group; X⁷ and X⁸ arethe same or different from each other, and represent a hydrogen atom, analkyl group, a nitro group, an amino or N-substituted amino group whichmay be protected by a protective group, a carboxyl group which may beprotected by a protective group, a hydroxymethyl group which may beprotected by a protective group, or an isocyanato group;

(i) when X⁵ is a carbamoyl group which may have a substituent, X⁶represents a carboxyl group, a substituted hydroxycarbonyl group, anamino group or N-substituted amino group which may be protected by aprotective group, or a nitro group;

(ii) when X⁵ is a nitro group, X⁶ represents a substitutedhydroxycarbonyl group;

(iii) when X⁵ is a substituted hydroxycarbonylamino group, X⁶ representsa substituted hydroxycarbonyl group, a hydroxymethyl group which may beprotected by a protective group, or an amino group which may beprotected by a protective group; and

(iv) X⁵ is a saturated aliphatic acylamino group or an aromaticacylamino group, X⁶ represents a carboxyl group, a hydroxymethyl groupwhich may be protected by a protective group, or an amino group whichmay be substituted by an alkyl group;

or a salt thereof.

The present invention provides a process for producing adiaminoadamantane derivative shown by the following formula (2j):

wherein X^(1j) and X^(2j) represent an amino group or N-substitutedamino group which may be protected by a protective group; and X³ and X⁴have the same meanings as defined above;

which comprises steps of

contacting a compound shown by the following formula (2h):

wherein X^(2h) represents a hydrogen atom or a nitro group; X³ and X⁴are have the same meanings as defined above; with a nitrogen oxide inthe presence of the imide compound shown by the formula (1), to producea dinitroadamantane derivative shown by the following formula (2i):

wherein X^(1i) and X^(2i) each represents a nitro group; and X³ and X⁴have the same meanings as defined above; and

reducing said dinitroadamantane derivative shown by the formula (2i) toproduce a corresponding diamino compound.

BEST MODE FOR CARRYING OUT THE INVENTION Imide Compound

In the compound shown by the formula (1), the halogenatom, as thesubstituents R¹ and R², includes iodine, bromine, chlorine and fluorineatoms. The alkyl group includes, for example, a straight chain orbranched chain alkyl group having about 1 to 10 carbon atoms such asmethyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl,pentyl, hexyl, heptyl, octyl, and decyl group. An illustrative preferredalkyl group includes alkyl groups having about 1 to 6 carbon atoms, inparticular lower alkyl groups having about 1 to 4 carbon atoms.

As the aryl group, there may be mentioned, for instance, a phenyl groupand a naphthyl group. Examples of the cycloalkyl group includecyclopentyl, cyclohexyl, and cyclooctyl groups. The alkoxy groupincludes, for example, an alkoxy group having about 1 to 10 carbon atomssuch as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy,t-butoxy, pentyloxy, andhexyloxy group. Among them, alkoxy groups havingabout 1 to 6 carbon atoms, in particular lower alkoxy groups havingabout 1 to 4 carbon atoms are preferable.

Examples of the alkoxycarbonyl group include an alkoxycarbonyl grouphaving about 1 to 10 carbon atoms in the alkoxy moiety such asmethoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl,butoxycarbonyl, isobutoxycarbonyl, t-butoxycarbonyl, pentyloxycarbonyl,and hexyloxycarbonyl group. A preferred alkoxycarbonyl group includesthose each having about 1 to 6 carbon atoms in the alkoxy moiety, inparticular lower alkoxycarbonyl groups each having about 1 to 4 carbonatoms in the alkoxy moiety.

The acyl group includes, for instance, an acyl group having about 1 to 6carbon atoms such as formyl, acetyl, propionyl, butyryl, isobutyryl,valeryl, isovaleryl, and pivaloyl group.

The substituents R¹ and R² may be either the same or different from eachother. In the formula (1), R¹ and R² may bond together to form a doublebond, or an aromatic or non-aromatic ring. A preferred aromatic ornon-aromatic ring may be a ring having about 5 to 12 members, inparticular about 6 to 10 members. Such a ring may be a heterocyclic ringor a condensed heterocyclic ring, and it may practically be ahydrocarbon ring. As such a ring, there may be mentioned, for instance,non-aromatic alicyclic rings (e.g., cycloalkane rings which may have asubstituent, such as cyclohexane ring, and a cycloalkene rings which mayhave a substituent, such as a cyclohexene ring), non-aromatic bridged(cross-linked) rings (e.g., bridged hydrocarbon rings which may have asubstituent, such as a 5-norbornene ring), aromatic rings which may havea substituent, such as a benzene ring, a naphthalene ring. The ring maypractically comprise an aromatic ring.

A preferred imide compound includes compounds shown by the followingformula:

where R³, R⁴ and R⁶ independently represent a hydrogen atom, an alkylgroup, a hydroxyl group, an alkoxy group, a carboxyl group, analkoxycarbonyl group, an acyl group, a nitro group, a cyano group, anamino group or a halogen atom; and R¹, R², Y and n have the samemeanings as defined above.

In the substituents R³, R⁴, R⁵ and R⁶, the alkyl group includes alkylgroups similar to those exemplified above, in particular alkyl groupseach having about 1 to 6 carbon atoms. The alkoxy group includes thesame alkoxy groups as mentioned above, in particular lower alkoxy groupseach having about 1 to 4 carbon atoms. Examples of the alkoxycarbonylgroup include the same alkoxycarbonyl groups as exemplified above, inespecial lower alkoxycarbonyl groups each having about 1 to 4 carbonatoms in the alkoxy moiety. As the acyl group, there may be mentionedthe similar acyl groups to those mentioned above, in particular acylgroups each having about 1 to 6 carbon atoms. Examples of the halogenatom include fluorine, chlorine and bromine atoms. The substituents R³,R⁴, R⁵ and R⁶ may practically be hydrogen atoms, lower alkyl groups eachhaving 1 to 4 carbon atoms, carboxyl groups, nitro groups or halogenatoms, respectively.

The symbol Y in the formula (1) denotes an oxygen atom or a hydroxylgroup, and n usually denotes about 1 to 3, preferably 1 or 2. Thecompound shown by the formula (1) can be used singly or in combinationof two or more in the nitration reaction.

As examples of the acid anhydride corresponding to the imide compound ofthe formula (1), there may be mentioned a saturated or unsaturatedaliphatic dicarboxylic acid anhydride such as succinic anhydride, maleicanhydride; a saturated or unsaturated nonaromatic cyclic polycarboxylicacid anhydride (an alicyclic polycarboxylic acid anhydride) such astetrahydrophthalic anhydride, hexahydrophthalic anhydride(1,2-cyclohexanedicarboxylic acid anhydride),1,2,3,4-cyclohexanetetracarboxylic acid 1,2-anhydride; a bridged cyclicpolycarboxylic acid anhydride (an alicyclic polycarboxylic acidanhydride) such as hetic anhydride, himic anhydride; an aromaticpolycarboxylic acid anhydride such as phthalic anhydride,tetrabromophthalic anhydride, tetrachlorophthalic anhydride,nitrophthalic anhydride, trimellitic anhydride,methylcyclohexenetricarboxylic anhydride, pyromellitic anhydride,mellitic anhydride, 1,8;4,5-naphthalenetetracarboxylic acid dianhydride.

Examples of a preferred imide compound include N-hydroxysuccinimide,N-hydroxymaleimide, N-hydroxyhexahydrophthalimide,N,N′-dihydroxycyclohexanetetracarboximide, N-hydroxyphthalimide,N-hydroxytetrabromophthalimide, N-hydroxytetrachlorophthalimide,N-hydroxyhetimide, N-hydroxyhimimide, N-hydroxytrimellitimide,N,N′-dihydroxypyromellitimide, N,N-dihydroxynaphthalene-tetracarboximideand so forth. A typically preferable imide compound includes anN-hydroxyimide compound derived from an alicyclic polycarboxylic acidanhydride, in particular from an aromatic polycarboxylic acid anhydride,such as N-hydroxyphthalimide.

The imide compound may be prepared by a conventional imidation process(a process for the formation of an imide), such as a process thatcomprises the steps of allowing a corresponding acid anhydride to reactwith hydroxylamine NH₂OH for ring-opening. of an acid anhydride group,and closing the ring to form the imide.

[Co-catalyst]

A catalyst may comprise the imide compounds of the formula (1) and aco-catalyst. The co-catalyst includes or comprises metal compounds suchas a compound comprising or containing a Group 2A element of thePeriodic Table of Elements (e.g., magnesium, calcium, strontium,barium), a transition metal compound, or compounds containing a Group 3Belement (e.g., boron B, aluminium Al) of the Periodic Table of Elements.These co-catalysts may be employed independently or in combination oftwo or more.

As the elements of the transition metal, there may be mentioned, forinstance, Group 3A elements of the Periodic Table of Elements (e.g.,scandium Sc, yttrium Y, and a lanthanoid element such as lanthanum La,cerium Ce, samarium Sm, an actinoid element such as actinium Ac), Group4A elements of the Periodic Table of Elements (e.g., titanium Ti,zirconium Zr, hafnium Hf), Group 5A elements (e.g., vanadium V, niobiumNb, tantalum Ta), Group 6A elements (e.g., chromium Cr, molybdenum Mo,tungsten W), Group 7A elements (e.g., manganese Mn, technetium Tc,rhenium Re), Group 8 elements (e.g., iron Fe, ruthenium Ru, osmium Os,cobalt Co, rhodium Rh, iridium Ir, nickel Ni, palladium Pd, platinumPt), Group 1B elements (e.g., copper Cu, silver Ag, gold Au) and Group2B elements (e.g., zinc Zn, cadmium Cd) of the Periodic Table ofElements.

A preferred element constituting the co-catalyst includes elements ofthe transition metals, for example, Group 3A elements of the PeriodicTable of Elements such as lanthanoid elements (e.g., Ce), actinoidelements; Group 4A elements such as Ti, Zr; Group 5A elements such as V,Nb; Group 6A elements such as Cr, Mo, W; Group 7A elements such as Mn,Tc, Re; Group 8 elements such as Fe, Ru, Co, Rh, Ni; or Group 1Belements such as Cu) and Group 3B elements such as B. The oxidationnumber of the metal elements constituting the co-catalyst is notparticularly limited, and may be, for example 0, +2, +3, +4, +5 and +6according to the variety of elements. The divalent transition metalcompounds (such as a divalent cobalt compound, a divalent manganesecompound) may be practically used as the co-catalyst.

The co-catalyst may be a simple substance or hydroxide of a metal. Theco-catalyst may practically be an a metal oxide (comprising a doubleoxide or an oxygen acid or a salt thereof) comprising the element, anorganic acid salt comprising the element, an inorganic acid saltcomprising the element, a halide comprising the element, a coordinatecompound (a complex) comprising the metal element, or a polyacid (aheteropolyacid or an isopolyacid) comprising the element or a saltthereof.

As the boron compound, there may be mentioned, for example, a boronhydride (e.g., borane, diborane, tetraborane, pentaborane, decaborane);aboric acid (e.g., orthoboric acid, metaboric acid, tetraboric acid); aborate (e.g., a nickel borate, magnesium borate, manganese borate);boron oxides such as B₂O₃; nitrogen-containing boron compounds such asborazane, borazene, borazine, boron amide, boron imide; halides such asBF₃, BCl₃, tetrafluoroborate; esters of boric acid (e.g., methyl borate,phenyl borate). A preferred boron compound includes boron hydrides andboric acids such as orthoboric acid or salts thereof, in particular aboric acid.

The hydroxide includes Mn(OH)₂, MnO(OH), Fe(OH)₂ and Fe(OH)₃, typicallyspeaking. Examples of the metallic oxide include Sm₂O₃, TiO₂, ZrO₂,V₂O₃, V₂O₅, CrO, Cr₂O₃, MoO₃MnO, Mn₃O₄, Mn₂O₃, Mno₂, Mn₂O₇, FeO, Fe₂O₃,Fe₃O₄, RuO₂, RuO₄, CoO, CoO₂, Co₂O₃, RhO₂, Rh₂O₃, Cu₂O₃. As examples ofthe double oxide or oxygen acid salt, there may be mentioned MnAl₂O₄,MnTiO₃, LaMnO₃, K₂Mn₂O₅, CaO.xMnO₂ (x=0.5, 1, 2, 3, 5), manganese salts[e.g., manganates (V) such as Na₃MnO₄, Ba₃(MnO₄)₂; manganates(VI) suchas K₂MnO₄, Na₂MnO₄, BaMnO₄; permanganates such as KMnO₄, NaMnO₄, LinO₄,NH₄MnO₄, CsMnO₄, AgMnO₄, Ca(MnO₄)₂, Zn(Mno₄)₂, Ba(MnO₄)₂, Mg(MnO₄)₃,Cd(MnO₄)₂].

As the organic acid salts, there may be exemplified as salts of a C₂₋₂₀fatty acid such as cobalt acetate, manganese acetate, cobalt propionate,manganese propionate, cobalt naphthenate, manganese naphthenate, cobaltstearate and manganese stearate, and manganese thiocyanate andcorresponding salts of Ce, Ti, Zr, V, Cr, Mo, Fe, Ru, Ni, Pd, Cu and Zn.The inorganic acid salt includes, for instance, nitrates such as cobaltnitrate, iron nitrate, manganese nitrate, nickel nitrate and coppernitrate, and sulfates, phosphates and carbonates each corresponding tothese nitrates (e.g., cobalt sulfate, iron sulfate, manganese sulfate,cobalt phosphate, iron phosphate, manganese phosphate, an ironcarbonate, a manganese carbonate, iron perchlorate). As the halides,there may be mentioned, for instance, chlorides such as SmCl₃, SmCl₂,TiCl₂, ZrCl₂ ZrOCl₂, VCl₃, VOCl₂, MnCl₂, MnCl₃, FeCl₂, FeCl₃, RuCl₃,CoCl₃, RhCl₂, RhCl₃, NiCl₂, PdCl₂, PtCl₂, CuCl and CuCl₂, or halidessuch as fluorides, bromides or iodides each corresponding to thesechlorides (e.g., MnF₂, MnBr₂, MnF₃, FeF₂, FeF₃, FeBr₂, FeBr₃, FeI₂CuBr,CuBr₂), complex halides such as M¹MnCl₃, M¹ ₂MnCl₄, M¹ ₂MnCl₅, M¹₂MnCl₆, wherein M¹ represents a monovalent metal.

The ligand constituting the complex includes, for example, OH (hydroxo);alkoxy groups such as methoxy, ethoxy, propoxy and butoxy group; acylgroups such as acetyl (OAc), propionyl group; alkoxycarbonyl groups suchas methoxycarbonyl (acetato), ethoxycarbonyl group; acetylacetonato(AA), cyclopentadienyl group; halogen atoms such as chlorine, bromine;CO, CN, oxygen atom, H₂O (aquo); phosphorus compounds such as aphosphine (e.g., triphenylphosphine and other triarylphosphine);nitrogen-containing compounds such as NH₃ (ammine), NO, NO₂ (nitro), NO₃(nitrato), ethylenediamine, diethylenetriamine, pyridine andphenanthroline. In the complexes or complex salts, the same or differentligands may be coordinated singly or in combination of two or more. Thepreferable ligand includes, for example, OH, an alkoxy group, an acylgroup, an alkoxycarbonyl group, acetylacetonato, a halogen atom, CO, CN,H₂O (aquo), triphenylphosphine and other phosphorus compounds, and anitrogen-containing compound inclusive of NH₃, NO₂and NO₃.

A preferable complex includes the complexes containing the preferabletransition metal element. The transition metal element and the ligandmay optionally be employed in combination to form a complex. Such acomplex includes, for instance, acetylacetonato complexes [e.g.,acetylacetonato complex of Ce, Sm, Ti, Zr, V, Cr, Mo, Mn, Fe, Ru, Co,Ni, Cu and Zn, titanylacetylacetonato complex TiO(AA)₂,zirconylacetylacetonato complex ZrO(AA)₂, vanadylacetylacetonato complexVO(AA)₂], cyano complexes [e.g., a hexacyanomanganate(I), ahexacyanoferrate(II)], carbonyl complexes or cyclopentadienyl complexes[e.g., tricarbonylcyclopentadienylmanganese(I),biscyclopentadienylmanganese(II), biscyclopentadienyliron(II), Fe(CO)₅,Fe₂(CO)₉, Fe₃(CO)₁₂], nitrosyl compounds [e.g., Fe(NO)₄, Fe(CO)₂(NO)₂],thiocyanato complexes [e.g., thiocyanatocobalt, thiocyanatomanganese,thiocyanatoiron], or acetyl complexes [e.g. cobalt acetate, manganeseacetate, iron acetate, copper acetate, zirconyl acetate ZrO(OAc)₂,titanyl acetate TiO(OAc)₂, vanadyl acetate VO(OAc)₂].

The polyacid is practically at least one member selected from Group 5elements or Group 6 elements of the Periodic Table of Elements, such asV (vanadic acid), Mo (molybdic acid) and W (tungstic acid), typicallyspeaking. There is no particular limit as to the central atom, and itmay be any of, for instance, Be, B, Al, Si, Ge, Sn, Ti, Zr, Th, N, P,As, Sb, V, Nb, Ta, Cr, Mo, W, S, Se, Te, Mn, I, Fe, Co, Ni, Rh, Os, Ir,Pt or Cu. As illustrative examples of the heteropolyacid, there may bementioned cobaltmolybdic acid, cobalttungstic acid, molybdenumtungsticacid, manganesemolybdic acid, manganesetungstic acid,manganesemolybdenumtungstic acid, vanadomolybdophosphoric acid,manganesevanadiummolybdic acid, manganesevanadomolybdophosphoric acid,vanadiummolybdic acid, vanadiumtungstic acid, silicomo-lybdic acid,silicotungstic acid, phosphomolybdic acid, phosphotangstic acid,phosphovanadomolybdic acid, and phosphovanadotangstic acid.

The catalysts have high activities. A combination of the catalyst withat least one reactant selected from (i) a nitrogen oxide and (ii) amixture of carbon monoxide and oxygen, accelerates a nitration and/orcarboxylation reaction of a substrate even in a mild or moderatecondition.

A catalyst comprising the imide compound shown by the formula (1) or theimide compound and the above co-catalyst may be whichever of ahomogeneous system or a heterogeneous system. The catalyst may be asolid catalyst comprising a catalytic component supported on a supportor carrier, as well. As the support, use can be practically made ofporous supports such as active carbon, zeolite, silica, silica-alumina,and bentonite. In the solid catalyst, the supporting amount of the imidecompound of the formula (1) as the catalyst component may be about 0.1to 50 parts by weight, preferably about 0.5 to 30 parts by weight andmore preferably about 1 to 20 parts by weight relative to 100 parts byweight of the support. The supporting amount more of the co-catalyst isabout 0.1 to 30 parts by weight, preferably about 0.5 to 25 parts byweight, and more preferably about 1 to 20 parts by weight, relative to100 parts by weight of the support.

Nitrogen Oxide

The nitrogen oxide may be shown by the formula:

N_(x)O_(y)

wherein x denotes an integer of 1 or 2 and y denotes an integer of 1 to6.

In the compound shown by the above formula, when x is 1, y is usually aninteger of 1 to 3; and when x is 2, y is usually an integer of 1 to 6.

Such nitrogen oxide may be exemplified N₂O, NO, N₂O₃, NO₂, N₂O₄, N₂O₅,NO₃ and N₂O₆. These nitrogen oxides may be used independently or incombination.

The preferred nitrogen oxide includes (i) a nitrogen oxide (particularlyN₂O₃) generated by the reaction of at least one nitrogen oxide selectedfrom dinitrogen oxide (N₂O) and nitrogen monoxide (NO) with oxygen, or anitrogen oxide containing N₂O₃ as a main component and (ii) a nitrogendioxide (NO₂) or a nitrogen oxide containing NO₂ as a main component.

Nitrogen oxide N₂O₃ may be easily obtained by a reaction of N₂O and/orNO with oxygen. To be more concrete, the nitrogen oxide may be preparedby introducing nitrogen monoxide and oxygen to a reactor to produce ablue liquid N₂O₃. Therefore, the nitration reaction may be carried outby introducing N₂O and/or NO and oxygen to a reaction system withoutproducing N₂O₃ in advance.

Incidentally, a pure oxygen may be used or may be distilled by an inertgas (e.g., carbon dioxide, nitrogen, helium and argon). Air may be usedas an oxygen source.

Mixture of Carbon Monoxide and Oxygen

Carbon monoxide or oxygen employed in the present invention may be pureone, and may be diluted with a inert gas (e.g., nitrogen, helium, argon,carbon dioxide). The oxygen source may be air. To the reaction system, amixture previously mixed carbon monoxide with oxygen may be introduced,and carbon monoxide and oxygen may separately introduced.

In the present invention, as a reactant, there may be employed, forexample, (i) the nitrogen oxide, (ii) the mixture of carbon monoxide andoxygen, or a combination of (i) the nitrogen oxide and (ii) the mixtureof carbon monoxide and oxygen. In the case of using (i) the nitrogenoxide as a reactant, a substrate is nitrated to generate a nitrocompound. In the case of using (ii) the mixture of the nitrogen monoxideand oxygen as the reactant, a substrate is carboxylated to generate acarboxyl compound. In the case of using (i) the nitrogen monoxide and(ii) the mixture of carbon monoxide and oxygen in combination as thereactant, a nitro compound and a carboxyl compound can be co-produced.In this case, use of a compound having plural reactive sites as asubstrate can provide a compound which has a nitro group and a carboxylgroup in the same molecule in one step by selecting a reaction condition(e.g., the ratio of the reactant (i) to (ii), a reaction temperature).

Substrate

Species of substrates is not particularly restricted, and may beemployed broad range of a saturated or unsaturated compound such as ahydrocarbon (e.g., an aliphatic hydrocarbon, an alicyclic hydrocarbon,an aromatic hydrocarbon), a heterocyclic compound, an alcohol, an ether,a ketone, an aldehyde, a carboxylic acid or derivative thereof, and thelike may be employed.

Preferred substrate comprises, for example, (a) a compound having amethyl group or a methylene group at the adjacent site of an unsaturatedbond, (b) a homo- or heterocyclic compound having a methylene group, (c)a compound having a methine carbon atom, (d) a compound having a methylgroup or a methylene group at the adjacent site of an aromatic ring and(e) a compound having a methyl group or a methylene group at theadjacent site of a carbonyl group. In the compound (b), the methylenegroup constitutes a 5- or 6-membered ring, and the compound (b) isusually a non-aromatic homo- or heterocyclic compound.

(a) The compound having a methyl group or a methylene group at theadjacent site of an unsaturated bond comprises an organic compoundhaving a double bond and/or a triple bond. Examples of such compoundsinclude propylene, 1-butene, 2-butene, butadiene, 1-pentene, 2-pentene,isoprene, 2-methyl-2-butene, 1-hexene, 2-hexene, 1,5-hexadiene,2,3-dimethyl-2-butene, 3-hexene, 1-heptene, 2-heptene, 1,6-heptadiene,1-octene, 2-octene, 3-octene, 1,7-octadiene, 2,6-octadiene, 1-nonene,2-nonene, decene, decadiene, dodecadiene, dodecatriene, undecene,undecadiene and undecatriene.

(b) Examples of the homocyclic compound (b1) having methylene groupinclude a cycloalkane (e.g., a cycloalkane having about 3 to 30 carbonatoms such as cyclopropane, cyclobutane, cyclopentane, cyclohexane,cycloheptane, methylcyclohexane, cyclooctane, 1,2-dimethylcyclohexane,cyclononane, isopropylcyclohexane, methylcyclooctane, cyclodecane,cyclododecane, cyclotridecane, cyclotetradecane, cyclopentadecane,cyclohexadecane, cyclooctadecane, cyclononadecane), a cycloalkene (e.g.,a cycloalkene having about 3 to 30 carbon atoms such as cyclopropene,cyclobutene, cyclopentene, cyclohexene, cycloheptene,1-methyl-1-cyclohexene, cyclooctene, cyclononene, cyclodecene,cyclododecene, limonene, menthene, menthone), a cycloalkadiene (e.g., acycloalkadiene having about 5 to 30 carbon atoms such ascyclopentadiene, cyclohexadiene, cycloheptadiene, cyclooctadiene,cyclodecadiene, cyclododecadiene), a cycloalkatriene (e.g.,cyclooctatriene), cycloalkatetraene (e.g., cyclooctatetraene) and acondensed polycyclic hydrocarbon.

(b) The heterocyclic compound (b2) having a methylene group comprises a5- or 6-membered cyclic compound having at least one hetero atomselected from nitrogen atom, oxygen atom and sulfur atom, or a condensedheterocyclic compound which is condensed by the 5- or 6-membered cycliccompound having the hetero atom at an aromatic ring, such asdihydrofuran, tetrahydrofuran, pyran, dihydropyran, tetrahydropyran,piperidine, piperadine, pyrrolidine, xanthene, and the like.

(c) The compound having a methine carbon atom (methylidine group)comprises, for instance, a chain hydrocarbon (c1) having a tertiarycarbon atom, a bridged cyclic hydrocarbon (c2) and the like.

Examples of the chain hydrocarbon (c1) having a tertiary carbon atominclude a aliphatic hydrocarbon having about 4 to 10 carbon atoms suchas isobutane, isopentane, isohexane, 3-methylpentane,2,3-dimethylbutane, 2-methylhexane, 3-methylhexane, 2,3-dimethylpentane,2,4-dimethylpentane, 2,3,4-trimethylpentane, 3-ethylpentane,2,3-dimethylhexane, 2,4-dimethylhexane, 3,4-dimethylhexane,2,5-dimethylhexane, 2-propylhexane, 2-methylheptane, 4-methylheptane,2-ethylheptane, 3-ethylheptane, 2,6-dimethylheptane, 2-methyloctane,3-methyloctane, 2,7-dimethyloctane and 2-methylnonane.

The bridged cyclic hydrocarbon (c2) comprises, for example, a bridgedcyclic hydrocarbon [e.g., bicyclo hydrocarbon such as decalin,hexahydroindan, carane, bornane, norbornene, norbornane, vinylnorborneneand norbornadiene; a tricyclo hydrocarbon such as homoblendane,adamantane and derivatives thereof (e.g., methyladamantane,1,3-dimethyladamantane, ethyladamantane, chloroadamantane, adamantanol,adamantanone, methyladamantanone, dimethyladamantanone,formyladamantanone), tricyclo[4.3.1.1^(2,5)]undecane; and atetracyclohydorocarbon such as tetracyclo[4.4.0.1.^(2,5).1.^(7,10)]dodecane], a dimer of a diene or hydrogen adduct thereof (e.g.,dicyclopentane, dicyclohxane, dicyclopentene, dicyclohexadiene,dicyclopentadiene, tetrahydrodicyclopentadiene) and a terpene (e.g.,pinane, pinene, camphor, bornene, caryophyllene).

The preferred compound (c) having a methine carbon atom includes abridged cyclic hydrocarbon having about 6 to 16 carbon atoms, inparticular about 7 to 14 (especially a bridged cyclic hydrocarbon suchas adamantane or a derivative thereof).

(d) Examples of the compound having a methyl group or a methylene groupat the adjacent site of an aromatic ring include an aromatic hydrocarbonhaving an alkyl group (e.g., toluene, o-, m- or p-xylene,1,2,3-trimethylbenzene, 1,2,4-trimethylbenzene, 1,3,5-trimethylbenzene(mesitylene), 1,2,3,4-tetramethylbenzene, 1,2,3,5-tetramethylbenzene,1,2,4,5-tetramethylbenzene (durene), 1,2,3,4,5,6-hexamethylbenzene,ethylbenzene, propylbenzene, cumene, o-, m- or p-ethyltoluene,butylbenzene, 1,4-diethylbenzene, 1-methylnaphthalene,2-methylnaphthalene, 1,5-dimethylnaphthalene, 2,5-dimethylnaphthalene,1-methylanthracene, 2-methylanthracene, 9-methylanthracene,dimethylanthracene, trimethylanthracene, 4,4′-dimethylbiphenyl,dibenzyl, diphenylmethane, triphenylmethane), an aromatic hydrocarbonhaving a cyclic methylene group (e.g., a condensed polycyclic aromatichydrocarbon condesed by a about 5 to 8 -membered ring, such as indane,indene, tetralin, dihydronaohthalene, fluorene, phenalene) and aheterocyclic compound having an alkyl group (e.g., a picoline such as2-methylfuran, 3-methylfuran, 2-methylpyran, 3-methylpyran,4-methylpyran, 3,4-dimethylpyran, 4-methylchroman, 6-methylchroman,2-methylpyridine, 3-methylpyridine and 4-methylpyridine, a lutidine suchas 2,3-dimethyipyridine, a collidine such as 2,4,6-trimethylpyridine,2-ethylpyridine, 3-ethylpyridine, 4-ethylpyridine, methylquinoline andmethylindole). The preferred compound (d) includes a compound having amethyl group or a methylene group at benzyl position.

(e) The compound having a (active) methyl group or methylene group atthe adjacent site of a carbonyl group comprises, for instance, analdehyde (e1), a ketone (e2) and a carboxylic acid or derivative thereof(e3).

The aldehyde (e1) comprises, for example, an aliphatic aldehyde (e.g.,an aliphatic monoaldehyde having about 2 to 12 carbon atoms such asacetaldehyde, propionaldehyde, butylaldehyde, isobutylaldehyde,pentylaldehyde, hexylaldehyde, heptylaldehyde, octylaldehyde,nonylaldehyde and decylaldehyde, an aliphatic polyaldehyde such asmalonaldehyde, succinaldehyde, adipic aldehyde and sebacic aldehyde), anaromatic aldehyde (e.g., benzaldehyde, anisaldehyde), an alicyclicaldehyde (e.g., formylcyclohexane, citronellal), a bridged cyclicaldehyde (e.g., formylnorbornene) and a heterocyclic aldehyde (e.g.,nicotinic aldehyde, furfural).

Examples of the ketone (e2) include an aliphatic ketone (e.g., acetone,methylethylketone, methylisopropylketone, methylisobutylketone,methyl-t-butylketone, 2-pentanone, 3-pentanone, 2-hexanone, 3-hexanone,2-heptanone, 3-heptanone, 4-heptanone, 2-octanone, 3-octanone,4-octanone, 2-nonanone and 2-decanone), a cyclic ketone (e.g., anon-aromatic cyclic mono- or polyketone such as cyclopentanone,cyclohexanone, methylcyclohexanone, dimethylcyclohexanone,cycloheptanone, isophorone, cyclooctanone, cyclononanone, cyclodecanone,cyclohexadione and cyclooctadione; a cyclic ketone having an aromaticring such as α-tetralone, β-tetralone and indanone), a bridged cyclicketone (e.g., pinocamphone, pinocarbon), an aromatic ketone (e.g.,acetophenene, propiophenone) and a heterocyclic ketone (e.g.,pyrrolidone, pyperidone).

The carboxylic acid or derivatives thereof (e3) comprises, for. example,an aliphatic dicarboxylic acid or dericatives thereof (e.g., malonicacid or an ester thereof, succinic acid or an ester thereof and glutaricacid or an ester thereof).

These substrates may be substituted by a suitable functional group, suchas a halogen atom, an oxo group, a hydroxyl group, an alkoxy group, acarboxyl group, an alkoxycarbonyl group, an acyl group, an alkyl group,an alkenyl group (e.g., an allyl group), a cycloalkyl group, an arylgroup, a vinyl group, an amino group, an alkylamino group, an amidogroup, a nitro group, a nitrile group, an acylamino group, a mercaptogroup, a sulfonyl group, a sulfinyl group, a sulfide group and aphosphino group.

In such substrates (a), (b), (c), (d) and (e), a nitro group or acarboxyl group can be introduced thereto at a carbon atom of a methyl ormethylene group, or a methine carbon atom. To be specific, a nitro groupor a carboxyl group can be smoothly introduced to the compound (c) at amethine carbon atom such as a cyclic methine carbon atom of the bridgedcyclic hydrocarbon to provide a nitro compound or a carboxy compound ofthe bridged cyclic hydrocarbonwithhighconversionandselectivity. Contactof, for example, adamantane among the bridged cyclic hydrocarbons withthe nitrogen oxide in the presence of the catalyst provides1-nitroadamantane and/or 1,3-dinitroadamantane and/or1,3,5-trinitroadamantane etc. Contact of adamantane with carbon monoxideand oxygen provides 1-carboxyadamantane and/or 1,3-dicarboxyadamantaneand/or 1,3,5-tricarboxyadamantane etc. Moreover, contact of adamantanewith the nitrogen oxide, carbon monoxide and oxygen in the presence ofthe catalyst provides 1-carboxy-3-nitroadamantane,1-carboxy-3,5-dinitroadamantane, 1,3-dicarboxy-5-nitroadamantane etc.Furthermore, contact of 1-methyladamantane with the nitrogen oxideprovides 1-methyl-3-nitroadamantane, contact of 1-methyladamantane withcarbon monoxide and oxygen provides 1-carboxy-3-methyladamantane etc.

In (d) the compound having a methyl group or a methylene group at anadjacent site of an aromatic ring, a nitro group or a carboxyl group canbe smoothly introduced thereto at the benzyl position. Contact of, forexample, toluene among the compound having a methyl group or a methylenegroup at the benzyl position with the nitrogen oxide in the presence ofthe catalyst provides nitrobenzene etc. and contact of toluene with thecarbon monoxide and oxygen provides phenylacetate. Use of ethylbenzeneas a substrate provides 1-nitroethylbenzene, 1-phenylpropionate etc.Application of the process of the present invention to fluorene provides9-carboxyfluorene.

Amount and Ratio of the Each Component

The amount of the imide compound shown by the formula (1) may beselected within a broad range, for example, of about 0.0001 mole (0.01mole %) to 1 mole (100 mole %), preferably about 0.001 mole (0.1 mole %)to 0.5 mole (50 mole %), more preferably about 0.01 to 0.30 mole, andmay be practically about 0.01 to 0.25 mole, relative to 1 mole of thesubstrate.

The amount of the co-catalyst may be selected within a broad range of,for example, about 0.0001 mole (0.01 mole %) to 0.7 mole (70 mole %),preferably about 0.0001 mole to 0.5 mole, more preferably about 0.001 to0.3 mole, andmaybe practically about 0.0005 to 0.1 mole (e.g., about0.005 to 0.1 mole), relative to 1 mole of the substrate.

The ratio of the co-catalyst to the imide compound shown by the formula(1) may be selected within the range not interfering with the reactionrate or selectivity, for example, of about 0.001 to 10 mole of theco-catalyst, preferably about 0.005 to 5 mole, more preferably about0.01 to 3 mole, andmay be practically about 0.01 to 5 mole, relative to1 mole of the imide compound.

The amount of the nitrogen oxide may be selected depending upon theintroduced amount of nitro group, within the range of, for example,about 1 mole or more (e.g., about 1 to 50 mole), preferably about 1.5 to30 mole, and may be usually about 2 to 25 mole, relative to 1 mole ofthe substrate.

The amount of carbon monoxide may be selected within the range of, forexample, about 1 mole or more (e.g., about 1 to 1000 mole), preferablyexcess mole, for example, about 1.5 to 100 mole (e.g., about 2 to 50mole), more preferably about 2 to 30 mole (e.g., about 5 to 25 mole),relative to 1 mole of the substrate.

The amount of oxygen may be selected within the range of about 0.5 moleor more (e.g., about 0.5 to 100 mole), preferably about 0.5 to 30 mole,more preferably about 0.5 to 25 mole, relative to 1 mole of thesubstrate.

In a continuous reaction, when excess amount of carbon monoxide andoxygen are used, they can be used to supply to the reaction systemcontinuously by, for example, circulating them.

The ratio of carbon monoxide (CO) to oxygen (O₂) may be selected withinthe wide range, as far as the amount of the each component is within theabove range, for example, of CO/O₂=about 1/99 to 99.99/0.01 (mole %)[e.g., about 70/30 to 99/1 (mole %)]. Use of more amount of the carbonmonoxide than that of oxygen is advantageous. The ratio of CO to O₂ maybe usually selected within the range of CO/O₂=about 1/99 to 99/1 (mole%) [e.g., about 10/90 to 99/1 (mole %)], and may be preferably about30/70 to 98/2 (mole %), more preferably about 50/50 to 95/5 (mole %),particularly about 60/40 to 90/10 (mole %).

The volume ratio of carbon monoxide to oxygen in a supply line may beselected within the range of, for example, CO/O₂=about 1/99 to99.99/0.01 (volume %) [e.g., about 70/30 to 99/1 (volume %)], and may beusually about 1/99 to 99/1 (volume %), preferably about 30/70 to 98/2(volume %), more preferably about 50/50 to 95/5 (volume %), specificallyabout 60/40 to 90/10.

Nitration Reaction and Carboxylation Reaction

The nitration reaction and/or the carboxylation reaction can beconducted in the presence or absence of a solvent. As the solvent, usecan be made of a solvent inert to reaction, examples of which areorganic acids (e.g., carboxylic acids such as acetic acid and propionicacid), nitriles (e.g., acetonitrile, propionitrile, benzonitrile),amides (e.g., formamide, dimethylformamide), alcohols (e.g., ethanol,propanol, butanol, t-butanol, t-amylalcohol), aliphatic hydrocarbons(e.g., hexane, octane), aromatic hydrocarbons (e.g., benzene), organichalogen compounds (e.g., halogenated hydrocarbons such asdichloromethane, chloroform, dichloroethane, dichlorobenzene, andtrifluoromethylbenzene; halogen-substituted carboxylic acids such aschloroacetic acid and trifluoroacetic acid; halogen-substituted acidanhydrides such as chloroacetic anhydride; halogen-substituted esterssuch as methyl chloroacetate and ethyl chloroacetate), nitro compounds(e.g., nitromethane, nitrobenzene), esters (e.g., ethyl acetate), ethers(e.g., dimethyl ether), and mixed solvents of these. Among them,carboxylic acids (e.g., acetic acid, propionic acid), organic halogencompounds and nitrites are preferred as the solvent. A mixture of two ormore solvents serves to enhance the yield and selectivity. As thesolvent mixtures, there may be mentioned a mixed solvent comprising atleast one solvent selected from nitriles and organic halogen compounds(e.g., amixed solvent of a nitrile and an organic halogen compound, amixed solvent of a nitrile and an organic acid), and the like. When thesolvents are used in combination, the ratio for blending these solventscan be selected from a wide range. For instance, the ratio of a dominantprimary solvent relative to the other solvent(s) ranges from about 1/99to 99/1 (the former/the latter, by weight), preferably from about 5/95to 95/5 (by weight), and more preferably about 10/90 to 90/10 (byweight) (e.g., 15/85 to 85/15 (by weight)).

In the present invention, the reactions can be smoothly conducted evenin a comparatively mild or moderate condition. The reaction temperaturemay be suitably selected according to species of the reactions, speciesof the imide compounds or the substrates. For example, in the nitrationreaction, the reaction temperature may be selected within the range ofabout 0 to 150° C., preferably about 25 to 125° C., more preferablyabout 30 to 100° C. The nitration reaction smoothly proceeds at acomparatively lower temperature such as within the range about 20 to 60°C. In the carboxylation reaction, the reaction temperature may beselected within the range of about 0 to 200° C., preferably about 10 to150° C. (e.g., about 10 to 120° C.), more preferably about 10 to 100° C.(e.g., about 10 to 80° C.). The reaction can be conducted under ambientpressure or in a pressure (under load).

When a nitrogen oxide is used as a reactant, a reaction in the presenceof oxygen sometimes provides a nitroalcohol or an alcohol. Thenitroalcohol is included in the nitro compound of the present invention.

The process of the present invention is useful for nitrating and/orcarboxylating a substrate to provide a nitro compound and/or carboxylcompound corresponding to the substrate, efficiently. In the process,the compound can be obtained with high conversion and selectivity evenin a mild and moderate condition. To be specific, when a mixture ofcarbon monoxide and oxygen is employed as a reactant a carboxyl groupcan be directly introduced to a substrate, and a carboxyl compoundhaving more carbon atoms than the substrate depending on the introducedamount of carboxyl groups. Thus, in the present invention, a substrateis contacted with carbon monoxide and oxygen in the presence of thecatalyst to provide a carboxyl compound at fewer reaction steps.

The reaction may be conducted in any of a batch, semi-batch, orcontinuous system. After the completion of the reaction, the reactionproduct can be easily separated and purified by a conventionalseparation/purification method including such separation methods asfiltration, concentration, distillation, extraction, crystallisation,recrystallisation, adsorption, column chromatography, and a combinationof these separation methods.

Adamantane Derivative

In the adamantane derivative shown by the formulas (2) and (3), aprotective group of a hydroxymethyl group (the moiety corresponding tohydroxyl group of hydroxymethyl group) is included, for instance,t-butyl group, a cycloalkyl group (e.g., cyclohexyl group), an aryl.group (e.g., 2,4-dinitrophenyl group), an aralkyl group (e.g., benzylgroup, 2,6-dichlorobenzyl group, 3-bromobenzyl group, 2-nitrobenzylgroup, 4-dimethylcarbamoylbenzyl group, a benzyl group which may have asubstituent such as triphenylmethyl group), tetrahydropyranyl group, anacyl group [e.g., a suturated aliphatic acyl group [(e.g., a saturatedC₂₋₆ aliphatic acyl group such as acetyl group, propionyl group,isopropionyl group, butyryl group, isobutyryl group, valeryl group,isovaleryl group, pyvaloyl group, preferably a C₂₋₄ saturated aliphaticacyl group), an aromatic acyl group (e.g., a C₇₋₁₃ aromatic acyl groupsuch as benzoyl group, p-phenylbenzoyl, phthaloyl, naphtoyl), analicyclic acyl group (a cycloalkyl-carbonyl group; such ascyclohexylcarbonyl)], an alkoxy carbonyl group such as aC₁₋₆alkoxy-carbonyl group (e.g., methoxy carbonyl group, ethoxy carbonylgroup, propyloxy carbonyl group, isopropyloxy carbonyl group,isobutyloxy carbonyl group, t-butyloxy carbonyl group), an alalkyloxycarbonyl group (e.g., benzyloxy carbonyl group, methoxybenzyloxycarbonyl group), a carbamoyl group, which may have a substituent such asa C₁₋₆alkyl group and a C₆₋₁₄aryl group, (e.g., carbamoyl group,methylcarbamoyl group, ethylcarbamoyl group, phenyl carbamoyl group), adialkylphosphinotioyl group (e.g., dimethylphosphinotioyl group), adiarylphosphinotioyl group (e.g., diophenylphosphinotioyl group). Apreferred protective group of hydroxymethyl group includes, forinstance, an acyl group (specifically, a saturated C₂₋₆aliphatic acylgroup etc., more specifically, a saturated C₂₋₄aliphatic acyl groupetc.), a C₁₋₆alkoxy-carbonyl group, a carbamoyl group which may have asubstituent.

A protective group of amino group includes, for example, as illustratedin the paragraph of the protective group of the hydroxyl group, t-butylgroup, an aralkyl group, a non-polymezable acyl group [such as asaturated aliphatic acyl group (e.g., a saturated C₂₋₆aliphatic acylgroup, especially, a saturated C₂₋₄aliphatic acyl group), an aromaticacyl group (e.g., a C₇₋₁₃aromatic acyl group), an alicyclic acyl group],an alkoxy carbonyl group (e.g., a C₁₋₆alkoxy carbonyl group), anaralkyloxy carbonyl group, a dialkylphosphinotioyl group, adiarylphosphinotioyl group. A preferred protective group of amino groupcomprises, for instance, a non-polymerizable acyl group [such as asaturated C₂₋₆aliphatic acyl group (specifically, a saturatedC₂₋₄aliphatic acyl group), a C₇₋₁₃aromatic acyl group], an alkoxycarbonyl group (specifically, a C₁₋₆alkoxy carbonyl group).

An N-substituted amino group includes, for example, a mono- ordi-C₁₋₆alkylamino group (e.g., methylamino group, ethylamino group, apropylamino group, dimethylamino group, diethylamino group),prefferably, a mono- or di-C₁₋₄alkylamino group.

A protective group of a carboxyl group comprises, for instance, analkoxy group such as a C₁₋₁₀alkoxy group (e.g., methoxy group, ethoxygroup, propoxy group, isopropoxy group, butoxy group, isobutoxy group,s-butoxy group, t-butoxy group, hexyloxy group), preferably, aC₁₋₆alkoxy group, especially, a C₁₋₄alkoxy group, a cycloalkyloxy group(e.g., cyclohexyloxy group), an aryloxy group (e.g., phenoxy group), anaralkyloxy group (e.g., benzyloxy group, diphenylmethyloxy group), atrialkylsilyloxy group (e.g., trimethylsilyloxy group), an amino groupwhich may have a substituent [amino group; an N-substituted amino group,such as a mono- or di-C₁₋₆alkyl amino group (e. g., methylamino group,dimethylamino group, ethylamino group, diethylamino group)], hydrazinogroup, an alkoxy carbonyl hydrazino group (e.g.,t-butoxycarbonylhydrazino group), an aralkyloxycarbonylhydrazino group(e.g., benzyloxycarbonylhydrazino group). A preferred protective groupof carboxyl group includes an alkoxy group (especially, a C₁₋₆alkoxygroup), an amino group which may have a substituent (e.g., anN-substituted amino group, especially, a mono- or di-C₁₋₆alkylaminogroup).

An alkyl group comprises, for instance, a C₁₋₆alkyl group, such asmethyl, ethyl, propyl, isopropyl, butyl, isoutyl, s-butyl, t-butyl,hexyl, preferrably, a C₁₋₄alkyl group, more preferably, methyl group orethyl group.

In the compound shown by the formula (3), a substituent of a carbamoylgroup includes, for example, a C₁₋₆alkyl group such as methyl, ethyl,propyl, butyl, and isobutyl group and a C₆₋₁₄aryl group such as phenyland naphthyl group. A substituted hydrooxycarbonylamino group includes,for example, a C₁₋₆alkoxy-carbonylamino group such asmethoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, andbutoxycarbonylamino group; a C₆₋₁₄aryloxy-carbonylamino group such asphenyloxycarbonylamino and naphtyloxycarbonylamino group; and aC₇₋₁₅aralkyloxy-carbonylamino group such as benzyloxycarbonylaminogroup.

Examples of a saturated aliphatic acylamino group include a saturatedC₂₋₆aliphatic acylamino group such as acetylamino, propionylamino,isopropionylamino, butylylamino, isobutylylamino, valerylamino,isovalerylamino, and pivaloylamino group, and preferably a saturatedC₂₋₄aliphatic acylamino group. An aromatic acylamino group includes, forexample, an aromatic C₇₋₁₃acylamino such as benzoylamino andnaphtoylamino group. A substituted oxycarbonyl group includes, forexample, a C₁₋₆alkoxy-carbonyl group such as methoxycarbonyl,ethoxycarbonyl, propoxycarbonyl and butoxycarbonyl group; aC₆₋₁₄aryloxy-carbonyl group such as phenyloxycarbonyl andnaphtyloxycarbonyl group; a C₇₋₁₅aralkyloxy-carbonyl group such asbenzyloxycarbonyl group. An alkyl group as a substituent of an aminogroup includes, for example, a C₁₋₆alkyl group such as methyl, ethyl,propyl, butyl and isobutyl group.

Examples of a preferred X¹ include nitro group, amino group, aC₂₋₆acylamino group corresponding to an amino group protected by aC₂₋₆acyl group, a C₁₋₆alkoxycarbonylamino group corresponding to anamino group protected by a C₁₋₆alkoxy-carbonyl group, carboxyl group, aC₁₋₁₀-alkoxy-carbonyl group corresponding to a carboxyl group protectedby a C₁₋₁₀loalkoxy group (especially, a C₁₋₆alkoxy-carbonyl group), acarbamoyl group, which may have a substituent, corresponding to acarboxyl group protected by an amino group which may have a substituent,hydroxymethyl group, isocyanato group. Examples of a preferred X²include amino group, a C₂₋₆acylamino group corresponding to an aminogroup protected by a C₂₋₆acyl group, a C₁₋₆alkoxy-carbonylamino groupcorresponding to an amino group protected by a C₁₋₆alkoxy-carbonylgroup, hydroxymethyl group, isocyanato group, depending on species ofX¹.

Examples of a preferred X³ or X⁴ include hydrogen atom, an alkyl group,nitro. group, amino group, a C₂₋₆acylamino group, aC₁₋₆alkoxy-carbonylamino group, carboxyl group, a C₁₋₁₀loalkoxy-carbonylgroup (particularly a C₁₋₆alkoxy-carbonyl group), a carbamoyl groupwhich may have a substituent, hydroxymethyl group and isocyanato group.

A preferred X⁵ includes, for example, a carbamoyl group which may have asubstituent, a C₁₋₆alkoxycarbonylamino group, a saturated aliphaticC₂₋₆acylamino group and an aromatic C₇₋₁₃acylamino group. A preferred X⁶includes, for example, carboxyl group, a C₁₋₁₀-alkoxycarbonyl group,amino group, a C₂₋₆acylamino group, a C₁₋₆alkoxy-carbonylamino group andnitro group, depending on species of X⁵.

A preferred X⁷ or X⁸ includes, for example, a substituent exemplified asthe preferred X³ or X⁴.

When such novel adamantane derivatives have an acidic group or a basicgroup, they may form salts.

Among the compounds 'shown by the formula (2), as a nitrogroup-containing adamantane derivative, there may be exemplified1-amino-3-nitroadamantane, 1-amino-3-methyl-5-nitroadamantane,1-amino-3,5-dimethyl-7-nitroadamantane, 1-amino-3,5-dinitroadamantane,1-methoxycarbonylamino-3-nitroadamantane,1,3-bis(methoxycarbonylamino)-5-nitroadamnatane,1-methoxycarbonylamino-3,5-dinitroadamantane,1-ethoxycarbonylamino-3-nitroadamantane,1-acetylamino-3-nitroadamantane, 1-acetylamino-3,5-dinitroadamantane,1,3-bis(acetylamino)-5-nitroadamantane,1-hydroxymethyl-3-nitroadamantane and 1-isocyanato-3-nitroadamantane.

As an adamantane derivative having an amino group or N-substituted aminogroup which may be protected by a protecting group, there may bementioned, for example, 1-amino-3-isocyanatoadamantane,1-amino-3-isocyanato-5-methyladamantane,1-isocyanato-3-methoxycarbonylaminoadamantane,1-isocyanato-3-(N-methylamino)adamantane and1-acetylamino-3-isocyanatoadamantane.

Examples of an adamantane derivative having a carboxyl group which maybe protected by a protecting group include1-carboxy-3-hydroxymethyladamantane,1,3-dicarboxy-5-hydroxymethyladamantane,1-carboxy-3,5-bis(hydroxymethyl)adamantane,1-carboxy-3-hydroxymethyl-5-methyladamantane,1-hydroxymethyl-3-methoxycarbonyladamantane,1-ethoxycarbonyl-3-hydroxymethyladamantane,1-hydroxymethyl-3-(N,N-dimethylcarbamoyl)adamantane,1-isocyanato-3-methoxycarbonyladamantane and1-isocyanato-3-(N,N-dimethylcarbamoyl)adamantane.

An adamantane derivative having a hydroxymethyl group which may beprotected by a protecting group includes, for example,1-acetyloxymethyl-3-isocyanatoadamantane and1-propionyloxymethyl-3-isocyanatoadamantane.

Among the adamantane derivatives shown by the formula (3), an adamantanederivative having a carbamoyl group which may have a substituentincludes, for example, 1-carboxy-3-(N-methylcarbamoyl)adamantane,1-carboxy-3-(N,N-dimethylcarbamoyl)adamantane,1-carboxy-3-methyl-5-(N,N-dimethylcarbamoyl)adamantane,1-methoxycarbonyl-3-(N,N-dimethylcarbamoyl)adamantane,1-amino-3-(N,N-dimethylcarbamoyl)adamantane,1-acetylamino-3-(N,N-dimethylcarbamoyl)adamantane,1-methoxycarbonylamino-3-(N,N-dimethylcarbamoyl)adamantane and1-(N,N-dimethylcarbamoyl)-3-nitroadamantane.

Examples of a nitro group-containing adamantane derivative include1-methoxycarbonyl-3-nitroadamantane,1,3-bis(methoxycarbonyl)-5-nitroadamantane,1-methoxycarbonyl-3,5-dinitroadamantane,1-methoxycarbonyl-3-methyl-5-nitroadamantane,1-ethoxycarbonyl-3-nitroadamantane, 1-nitro-3-propoxycarbonyladamantaneand 1-nitro-3-phenoxycarbonyladamantane.

A substituted hydroxycarbonylamino group-containing adamantanederivative includes, for example,1-methoxycarbonyl-3-methoxycarbonylaminoadamantane,1-methoxycarbonyl-3-methoxycarbonylamino-5-methyladamantane,1-ethoxycarbonyl-3-ethoxycarbonylaminoadamantane,1-hydroxymethyl-3-methoxycarbonylaminoadamantane,1-amino-3-methoxycarbonylaminoadamantane,1-amino-3-methoxycarbonylamino-5-methyladamantane,1-acethylamino-3-methoxycarbonylaminoadamantane and1-acetylamino-3-ethoxycarbonylaminoadamantane.

A saturated aliphatic or aromatic amino group-containing adamantanederivative includes, for example, 1-acetylamino-3-carboxyadamantane,1,3-bis(acetylamino)-5-carboxyadamantane,1-acetylamino-3,5-dicarboxyadamantane,1-acetylamino-3-carboxy-5-methyladamantane,1-benzoylamino-3-carboxyadamantane,1-acetylamino-3-hydroxymethyladamantane,1-acetylamino-3-aminoadamantane, 1,3-bis(acetylamino)-5-aminoadamantane,1-acetylamino-3,5-diaminoadamantane,1-acetylamino-3-(N,N-dimethylamino)adamantane and1-acetylamino-3-(N-methylamino)adamantane.

The adamantane derivative shown by the formula (2) or (3) may have othersubstituents, for example, a halogen atom, an oxo group, a hydroxyalkylgroup (e.g., hydroxy C₂₋₄alkyl groups such as 2-hydroxyethyl group), anacyl group (e.g., C₁₋₆acyl groups such as formyl, acetyl, propionyl,butyryl, isobutyryl, valeryl, isovaleryl and pivaloyl group), analkoxycarbonyl group (e.g., C₁₋₆alkoxy-carbonyl group such asmethoxycarbonyl, ethoxy-carbonyl, propoxycarbonyl, isopropoxycarbonyl,butoxycarbonyl, isobutoxycarbonyl, t-butoxycarbonyl and hexyloxycarbonylgroup) and cyano group.

Production of Adamantane Derivatives

The adamantane derivatives shown by the formulas (2) and (3) and anadamantane derivative having at least two substituents selected from thegroup consisting of a nitro group, an amino group or N-substituted aminogroup which may be protected by a protecting group, a carboxyl groupwhich may be protected by a protecting group, a hydroxymethyl groupwhich may be protected by a protecting group, and an isocyanato group,at a methine carbon atom of a bridgehead position of adanantane skeltoncan be obtained by the foll owing reaction step scheme (I) or (II), orby combinating the reaction step scheme (I) and (II).

wherein X^(1b) represents a nitro group; X^(1c) represents an aminogroup; X^(1d) represents an isocyanato group; X^(2a), X^(2b), X^(2c) andX^(2d) represent a hydrogen atom, a nitro group, an amino orN-substituted amino group which may be protected by a protecting group,a carboxyl group which may be protected by a protecting group, ahydroxymethyl group which may be protected by a protecting group, or anisocyanato group respectively; and X³ and X⁴ respectively have the samemeanings as defined above).

wherein X^(1f) represents a carboxyl group; X^(1g) represents ahydroxymethyl group; X^(2e), X^(2f) and X^(2g) represents a hydrogenatom, a nitro group, an amino or N-substituted amino group which may beprotected by a protecting group, a carboxyl group which may be protectedby a protecting group, a hydroxymethyl group which may be protected by aprotecting group, or an isocyanato group; and X³ and X⁴ each has thesame meanings as defined above.)

The nitration (nitration reaction which derives compound (2b) fromcompound (2a)) of the step (I-1) in the reaction step scheme (I) may becarried out by the nitration method, i.e., the method of contacting asubstrate with a nitrogen oxide at least, in the presence of the imidecompound shown by the formula (1). A nitro group can be introduced to amethine carbon atom of a bridgehead position by the nitration. WhenX^(2a) in the compound (2a) is hydrogen atom, X^(2a) may be alsoconverted into a nitro group according to reaction conditions. Forexample, nitration of an adamantane may give 1-nitroadamantane and/or1,3-dinitroadamantane. Further, the nitration of 1-nitroadamantane,1-carboxyadamantane and 1-hydroxyadamantane may give1,3-dinitroadamantane, 1-carboxy-3-nitroadamantane and1-hydroxy-3-nitroadamantane, respectively.

The reduction (reductive reaction which derives compound (2c) fromcompound (2b)) of the step (I-2) may be carried out by a conventionalmethod such as catalytic hydrogenation process using hydrogen as areducing agent and reduction process using a hydrogenation reducingagent.

In the catalytic hydrogenation, a simple substance of a metal such asplatinum, palladium, nickel, cobalt, iron and copper, a compoundcontaining such metal elements (e.g., platinum oxide, palladium black,palladium carbon and copper chromite) or the like may be used as acatalyst. The amount of the catalyst is practically about 0.02 to 1 molerelative to 1 mole of a substrate. Further, in a catalytichydrogenation, the reaction temperature may be, for example, about −20to 100° C. (e.g., about 0 to 90° C.). A hydrogen pressure is practicallyabout 1 to 100 atm (e.g., about 1 to 50 atm).

In the reducing process using a hydrogenation reducing agent, thehydrogenation reducing agent to be used includes, for example, aluminiumhydride, lithium aluminium hydride, lithium trialkoxyaluminium hydride,sodium boron hydride, diborane, bis-3-methyl-2-butylborane, ametal(e.g., zinc, tin, iron) acid, a sulfide and hydrazine. The reducingprocess using a hydrogenation reducing agent may be conducted also inthe presence of a Lewis acid such as aluminium chloride anhydride andboron trifluoride. The amount of the hydrogenation reducing agent isusually about 1 mole or more (e.g., about 1 to 10 mole) relative to 1mole of a substrate. In the reducing process using the hydrogenationreducing agent, a reaction temperature is practically about 0 to 200° C.(e.g., about 0 to 170° C.).

Incidentally, the reduction reaction (the catalytic hydrogenation andthe process using the hydrogenation reducing agent) may be carried outin the presence of a solvent inert to the reduction reaction (e.g., analcohol such as methanol and further a solvent exemplified in thenitration reaction such as a carboxylic acid, an ether, an ester and anamide). Moreover, when reduction reaction is conducted by the catalytichydrogenation, an acid such as hydrochloric acid may be added to thereaction system in order to improve the catalytic activity.

The nitro group X^(1b) of the compound (2b) is converted into an aminogroup by the reduction reaction. In the compound (2b), when X^(2b) is anitro group, the nitro group may be also converted into an amino groupaccording to reaction conditions. For example, the reduction of1-nitroadamantane may give 1-aminoadamantane, and the reduction of1,3-dinitroadamantane may give 1-amino-3-nitroadamantane and/or1,3-diaminoadamantane. Further, the each reduction of1-carboxy-3-nitroadamantane and 1-hydroxymethyl-3-nitroadamantane maygive 1-amino-3-carboxyadamantane and 1-amino-3-hydroxymethyladamantanerespectively.

The isocyanation (reaction deriving compound (2d) from compound (2c)) ofthe step (I-3) may be carried out by a conventional method, for example,the method using phosgene. The reaction of the compound (2c) withphosgene may be conducted, for example, in the presence or absence of asolvent at a temperature of about −10 to 100° C. The amount of phosgeneis, for example, about 0.8 to 10 mole and preferably about 1 to 2 molerelative to 1 mole of the compound (2c).

The amino group X^(1c) of the compound (2c) may be converted into anisocyanato group by the reaction mentioned above. When X^(2c) of thecompound (2c) is an amino group, the amino group may be converted intoan isocyanato group according to conditions. For example, theisocyanation of 1-aminoadamantane may give 1-isocyanatoadamantane.Further, each of 1-amino-3-nitroadamantane, 1.3-diaminoadamantane,1-amino-3-carboxyadamantane and 1-amino-3-hydroxymethyladamantane may besubjected to isocyanation to give 1-isocyanato-3-nitroadamantane,1,3-diisocynatoadamantane, 1-isocyanato-3-carboxyadamantane and1-isocyanato-3-hydroxymethyladamantane respectively.

The carboxylation (reaction deriving compound (2f) from compound (2e))of the step (II-1) in the reaction step scheme (II) may be carried outby the above-mentioned carboxylation, i.e., the process for contacting asubstrate with at least carbon dioxide and oxygen in the presence of theimide compound shown by the formula (1). A carboxyl group can beintroduced to a methine carbon atom at a bridgehead position of thecompound (2e) by the carboxylation. When X^(2e) of the compound (2e) isa hydrogen atom, X^(2e) may be also converted to a carboxyl groupaccording to reaction conditions. For example, an adamantane may becarboxylated to produce 1-carboxyadamantane and/or1,3-dicarboxyadamantane as previously described. Further, thecarboxylation of each 1-carboxyadamantane and 1-nitroadamantane may give1,3-dicarboxyadamantane and 1-carboxy-3-nitroadamantane respectively.

The reduction (reaction introducing compound (2g) from compound (2f)) ofthe step (II-2) may be carried out by a conventional method such ascatalytic hydrogenation using hydrogen as a reducing agent and a methodusing a hydrogenation reducing agent described for the step (I-2). Inthis step, a preferred hydrogenation reducing agent includes, forexample, a sodium boron hydride-Lewis acid, aluminum hydride, lithiumaluminum hydride, lithium trialkoxyaluminum hydride and diborane.

The reduction reaction may convert the carboxyl group X^(1f) of thecompound (2f) may be converted to a hydroxymethyl group. Moreover, whenX^(2f) of the compound (2f) is a carboxyl group, the carboxyl group maybe also converted to a hydroxymethyl group according to reactionconditions. For example, the reduction of 1-carboxyadamantane gives1-hydroxymethyladamantane, and the reduction of 1,3-dicarboxyadamantanegives 1-carboxy-3-hydroxymethyladamantane and/or1,3-bis(hydroxymethyl)adamantane.

Incidentally, according to the species of substrates, a hydroxylmethylgroup (a site corresponding to a hydroxyl group of the hydroxymethylgroup), an amino group and a carboxyl group of the reaction component orthe reaction product may be protected by the above protecting groupbefore, after, or during the each step. The introduction and eliminationof the protecting group for a hydroxymethyl group, an amino group and acarboxyl group may be carried out by a conventional method such asesterification, amidation, carbamation, carbonation, hydrolysis andhydrogenolysis, if necessary, using an acid, an alkali, an ion-exchangeresin, a catalyst for hydrogenolysis or the like.

When an acyl group is.used as a protecting group for a hydroxylmethylgroup or an amino group (acyloxymethyl group or acylamino group isformed), the hydroxymethyl group or the amino group of the substrate maybe protected by allowing to act an acylating agent on the substrate.Examples of the acylating agent include C₂₋₆aliphatic monocarboxylicacids such as acetic acid, propionic acid, n-butyric acid, isobutyricacid, valeric acid and pivalic acid (preferably C₂₋₄carboxylic acids),and reactive derivatives thereof [e.g., acid anhydrides such as aceticanhydride and valeic anhydride, acid halides such as acid chloride(e.g., acetyl chloride, propionyl chloride and butyryl chloride)]. Whenan acid anhydride or an acid halide is used as an acylating agent, theacylation reaction is usually carried out in the presence of a base inorder to capture the acid which is a by-product in the reaction. As thebase, there may be exemplified an inorganic base (e.g., a hydroxide ofan alkai metal such as sodium hydroxide; a hydroxide of alkaline earthmetal such as barium hydroxide; carbonate of an alkaline metal such assodium carbonate; a carbonate of an alkaline earth metal such as bariumcarbonate; a hydrogencarbonate of an alkaline metal such as sodiumhydrogencarbonate); and an organic base (e.g., a tertiary amine such astriethylamine and N-methylpiperidine; a basic heterocyclic compoundcontaining a nitrogen atom such as pyridine; an alkoxide of an alkalimetal such as sodium methoxide and sodium ethoxide). The acylating agentmay be used singly or in combination of two or more.

For example, 1-acetylamino-3-nitroadamantane can be obtained by actingacethyl chloride on 1-amino-3-nitroadamantane in the presence of thebase.

When a substituted hydroxycarbonyl group is used as a protecting groupfor a hydroxymethyl group or an amino group, the hydroxyl group or theamino group may be protected by reacting a substrate with ahalocarbonate to obtain a compound having a carbonate group or carbamategroup. The reaction may be usually carried out in the presence of abase. As the base, the similar base to one exemplified above may beused.

When a carbamoyl group is used as a protecting group for a hydroxymethylgroup, the hydroxymethyl group may be protected, for example, byreacting a substrate with an isocyanate compound, if necessary, in thepresence of the base exemplified above to obtain a compound having acarbamoyloxy group.

Moreover, an adamantane derivative having N-substituted amino group maybe produced, for example, by reacting a substrate with a hydrocarbonhalide (e.g., aliphatic hydrocarbon halide such as iodomethane,iodoethane, iodobutane, bromomethane, bromoethane, bromobutane,chloromethane and chloroethane). The reaction may be conducted in thepresence of a de-hydrogen halide agent (an agent for eliminating ahydrogen halide). As the de-hydrogen halide agent, a base, for example,the above exemplified may be practically used. The reaction may beconducted in solvent inert to the reaction. As such solvent, use may bemade of exemplified solvents for the nitration reaction such as ahydrocarbon halide, an ether, an ester and an amide.

When a substituted hydroxyl group (e.g., an alkoxy group) protects acarboxyl group [(i.e., when a substituted hydroxycarbonyl group (anester group)] is formed), the carboxyl group may be protected byreacting a carboxyl group-containing compound or derivative thereof(e.g., an acid halid such as an acid chloride) with an alcohol (e.g.,methanol, ethanol) or reactive derivative thereof (e.g., lower alkylester), if necessary, in the presence of an acid (e.g., a mineral acidsuch as hydrochloric acid and sulfuric acid) or an base (e.g., the baseexemplified above) to produce a compound having the corresponding estergroup. The lower alkyl ester inclu des, for example, aceticacid-C₁₋₄alkyl ester such as methyl acetate and ethyl acetate or thecorresponding propionate (e.g., methyl propionate, ethyl propionate).For example, 1-methoxycarbonyl-3-nitroadamantane may be obtained byreacting 1-carboxy-3-nitroadamantane with methanol in the presence of anacid, or by acting thionyl chloride on 1-carboxy-3-nitroadamantanefollowed by reacting with methanol in the presence of a base.

Moreover, when a carboxyl group is converted into a group having anamide bond with use of an amino group as a protecting group for thecarboxyl group (i.e., when an N-substituted or unsubstituted carbamoylgroup is formed), a condition of a conventional process for forming anamido bond may be applied. The process for forming an amido bond may becarried out, for example, by following methods:

(a) a method by a mixed acid anhydride, i.e., a method which comprisesreacting a compound having a carboxyl group with an acid halide (e.g.,acetyl chloride, propionyl chloride, acetyl bromide) to produce a mixedacid anhydride followed by reacting the given mixed acid anhydride withan amine compound;

(b) a method by an active ester, i.e., a method which comprisesconverting a substrate into an active ester thereof, such asp-nitrophenylester, an ester with N-hydroxysuccinimide, an ester with1-hydroxybenzotriazol or the like followed by reacting the given esterwith an amine compound;

(c) a method by a carbodiimide, i.e., a method which condenses an aminecompound with a substrate in the presence of an activating agent such asdicyclohexylcarbodiimide and carbonyldlimidazol; or

(d) a method which comprises converting a substrate into a carboxylicanhydride thereof by a dehydrator such as acetic anhydride followed byreacting the given carboxylic anhydride with an amine compound, or amethod which comprises converting a substrate to an acid halide thereoffollowed by reacting the acid halide with an amine compound.

The amine compound used in the amide bond forming reaction includes, forexample, ammonia or a derivative thereof (e.g., ammonium halide such asammonium chloride), a primary amine, a secondary amine, hydrazine or aderivative thereof (e.g., alkoxycarbonylhydrazine such ast-butoxycarbonylhydrazine, alkoxycarbonylhydrazine such asbenzyloxycarbonylhydrazine).

For example, the reaction of an acid halide with an amine compound maybe carried out in a suitable solvent, in the presence of an basiccompound. As the basic compound, use may be made of a basic compoundexemplified for the reaction of the compound (Ia) having an amino groupor the compound (1d) with a hydrocarbon halide and the like.

Moreover, as the solvent, an organic solvent (e.g., an ether, an ester,an amide) exemplified for the nitration reaction may be employed.

Furthermore, the compound having a carbamoyl group may be obtained byreacting a compound having an ester group (e.g., an alkoxycarbonylgroup, an aryloxycarbonyl group, an aralkyloxycarbonyl group) as aprotected carboxyl group with the amine compound in the presence of acatalyst comprising a metal compound.

Examples of the metal compound used in the reaction (the amidationreaction) include a conventional catalyst for transesterification(including a catalyst for transferring an ester to an amide), forexample, a transition metal compound such as a compound comprising Group3B element of the Periodic Table of Elements (e.g., aluminum compoundsuch as AlCl₃), a compound comprising Group 4A element of the PeriodicTable of Elements (e.g., titanium compound such as TiCl₄), a compoundcomprising Group 3A element (e.g., samarium compound such as SmI₂) ofthe Periodic Table of Elements.

The amount of the catalyst may be liberally selected within a broadrange, for example, about 0.1 mole % to 1 equivalent, preferably about0.5 to 50 mole %, and more preferably about 1 to 25 mole % (e.g., about5 to 20 mole %) relative to a compound having an ester group.

The ratio of the amine compound to the ester group-containing compoundis, for example, about 0.5 to 5 mole, preferably about 0.8 mole or more(e.g., about 0.8 to 5 mole), and specifically about 1 mole or more(e.g., about 1 to 3 mole, in particular about 1 to 1.5 mole) of ammoniaor the like relative to 1 equivalent of the ester group-containingcompound.

The amidation reaction may be carried out in the presence or absence ofa solvent inert to the reaction. As the reaction solvent, there may beexemplified an aliphatic hydrocarbon, an alicyclic hydrocarbon, anaromatic hydrocarbon, a ketone, an ether, a non-protonic polar solventand a mixture thereof. The reaction temperature may be selected withinthe range of, for example, about 0 to 150° C., and preferably about 25to 120° C.

The adamantane derivative shown by the formula (2) and (3) of thepresent invention can be concretely produced as follows.

For example, among compounds shown by the formula (2), a compound havinga nitro group and an amino group which may have a protecting group or asubstituent can be produced through the steps (I-1) and (I-2). Acompound having a nitro group and an isocyanato group can be producedthrough the steps (I-1), (I-2) and (I-3). A compound having a nitrogroup and a hydroxymethyl group which may be protected by a protectinggroup may be obtained through the steps (I-1), (II-1) and (II-2).

A compound having an amino group which may have a protective group or asubstituent, and an isocyanato group may be produced through the steps(I-1), (I-2) and (I-3).

A compound having a carboxyl group, which may be protected by protectivegroup, and a hydroxymethyl group which may be protected by a protectinggroup may be obtained, for example, through the step (II-1) and (II-2).A compound having a carboxyl group which may be protected by aprotecting group, and an isocyanato group may be obtained through thesteps (I-1), (I-2), (I-3) and (II-1).

A compound having a hydroxylmethyl group which may be protected by aprotecting group, and an isocyanato group may be produced through thesteps (I-1), (I-2), (I-3), (II-1) and (II-2).

Among the compounds shown by the formula (3), a compound having acarbamoyl group which may have a substituent, and a carboxyl group maybe obtained through the step (II-1) and the step of introducing an aminogroup to a carboxyl group (the amide group-forming step). A compoundhaving a carbamoyl group which may have a substituent, and a substitutedhydroxycarbonyl group may be obtained through the step (II-1), the stepfor introducing an amino group to a carboxyl group and the step forintroducing a substituted hydroxyl group to another carboxyl group (theester group-forming step). A compound having a carbamoyl group which mayhave a substituent, and an amino group which may have a protecting groupor a substituent may be obtained through the steps (I-1), (I-2), (II-1)and the step of introducing an amino group to the carboxyl group. Acompound having a carbamoyl group which may have a substituent, and anitro group may be obtained through the steps (I-1), (II-1) and the stepof introducing an amino group to the carboxyl group.

A compound having a nitro group and a substituted hydroxycarbonyl groupmay be produced through the steps (I-1), (II-1), and the step ofintroducing a substituted hydroxyl group to the carboxyl group. Acompound having a substituted hydroxycarbonylamino group and asubstituted hydroxycarbonyl group may be obtained through the steps(I-1), (I-2), (II-1) and the step of introducing the substitutedhydroxycarbonyl group to an amino group (the carbamate group-formingstep) and the step of introducing a substituted hydroxyl group to thecarboxy group. A compound having a substituted hydroxycarbonylaminogroup and, a hydroxyl group may be protected by a protecting groupthrough the steps (I-1), (I-2), (II-1), (II-2), and the step ofintroducing an amino group to the substituted hydroxycarbonyl group. Acompound having a substituted hydroxycarbonylamino group and an aminogroup which may be protected by a protecting group may be obtainedthrough the steps (I-1), (I-2), (I-3), and the step of introducing ansubstituted hydroxycarbonyl group to the amino group. A compound havinga saturated aliphatic or aromatic acylamino group and a carboxylg roupmay be obtained through the steps (I-1), (I-2), (II-1), and the step ofintroducing an acyl group to an amino group. A compound having asaturated aliphatic or aromatic acylamino group and a hydroxylmethylgroup which may be protected by a protectinggroupmaybeobtainedthroughthesteps (I-1), (I-2), (II-1), (II-2), and thestep of introducing an acyl group to an amino group. A compound having asaturated aliphatic or aromatic acylamino group and an amino group whichmay be protected by an alkyl group may be obtained through the steps(I-1), (I-2), and the step of introducing an acyl group to an aminogroup. The introduction of an amino group or a substituted hydroxylgroup to a carboxyl group, introduction of a substituted hydroxycarbonylgroup to an amino group, and introduction of an acyl group to an aminogroup may be carried out by the above method for introducing aprotecting group.

Further, the diaminoadamantane derivative (compound (2j)) having atleast two groups of amino groups or N-substituted amino groups, whichmay be protected by a protecting group, at bridgehead position ofadamantane skeleton may be obtained by nitrating the compound (compound(2h)) in which X^(2a) of the compound (2a) is a hydrogen atom or a nitrogroup according to the step (I-1) to form a dinitro body (compound (2i))in which X^(1b) and X^(2b) of the compound (2b) are nitro groups, andthen reducing it according to the step (I-2) to convert into a diaminobody in which X^(1c) and X^(2c) of the compound (2c) are an amino groupsand, if necessary, introducing a protecting group or a substituent tothe amino group. In the method, since the diamino body is directlyformed in the form of not salt but free, the alternation ordenaturation, decomposition or decrease of recover efficiency, eachoccuring when salt of a diamino body becomes free may be avoid.Therefore, the diamino adamantane derivative may be efficiently producedwith high yield.

INDUSTRIAL APPLICABILITY

In the method of the present invention, a substrate may be directlynitrated and/or carboxylated efficiently even in a mild or moderatecondition since an imide compound shown by the formula (1) is combinedwith at least one reacting agent selected from (i) a nitrogen oxide and(ii) a mixture of carbon monoxide and oxygen. Moreover, to a substrate,at least one functional group selected from a nitro group and a carboxylgroup can be introduced to produce a nitro compound and/or carboxycompound with high conversion and selectivity even in the mild ormoderate condition.

Moreover, nitrogen oxide, which causes environmental pollution, isefficiently utilized to form a nitro compound may be produced with highconversion and selectivity. Further, a carboxy compound having morecarbon atoms than that of a substrate may be efficiently produced by asimple operation through fewer steps.

Further, in the present invention, a novel adamantane derivative usefulfor a high functional material may be provided. A diamino body ofadamantane can be produced in high yield.

EXAMPLES

The following examples are intended to describe this invention infurther detail and should by no means be interpreted as defining thescope of the invention. Incidentally, infrared absorption spectra weremeasured after purifying the reaction product by column chromatography.

Example 1

Into a flask, 1 mmole of adamantane, 0.05 mmole of N-hydroxyphthalimideand 5 ml of acetic acid were added to mix and then the flask wasequipped with a gas bag (about 1L) of nitrogen monoxide NO. The mixturewas reacted for 8 hours at 100° C. with stirring. The reaction productswere analyzed by gas chromatography, and, as a result, The conversion ofadamantane was 95%, and nitroadamantane (yield 30%), adamantanol (yield17%) and acetyloxyadamantane (yield 33%) were formed.

Examples 2 to 5

Into a flask, 1 mmole of adamantane, 0.05 mmole of N-hydroxyphthalimideand 5 ml of the solvent represented in Table 1 were added to mix, andthen the flask was equipped with a gas bag (about 1L) of nitrogenmonoxide NO. The mixture was heated to 100° C. with stirring. After theperiod of time shown in Table 1, the reaction products were analyzed bygas chromatography, and, as a result, nitro compounds were formed withconversions and yields represented in Table 1.

TABLE 1 Yields(%) Sol- Times Conver- Com. Com. Com. Com. Com. vents (hr)sions(%) 1 2 3 4 5 Ex.2 BzCN 5 76 16 0 19 9 8 Ex.3 AcOH 10 95 11 22 2010 10 Ex.4 AcOH 16 99 4 17 30 15 18 Ex.5 DCE 16 64 19 0 18 6 4 BzCN:benzonitorile AcOH: acetic acid DCE: dichloroethane Com. 1: adamantanolCom. 2: acetyloxyadamantane Com. 3: nitroadmantane Com. 4:adamantanediol Com. 5: nitroadamantano

Examples 6 to 8

Into a flask, 1 mmole of adamantane, 0.05 mmole of N-hydroxyphthalimideand 5 ml of the solvent shown in Table 2 were added to mix and the flaskwas purged by nitrogen monoxide NO (about 1L) and oxygen O₂ (about 1L).The mixture was reacted for 10 hours at the temperatures shown in Table2, with stirring. Reaction products were analyzed by gas chromatography,and, as a result, nitro compounds were formed with yields represented inTable 2.

Meanings of the symbols shown in Table 2 are as follows.

TABLE 2 Temperatures Conver- Yields(%) Solvents (° C.) sions(%) Com.1Com.2 Com.3 Com.4 Com.5 Ex.6 AcOH 100 99 4 11 43 10 21 Ex.7 AcCN + DCE60 89 5 10 50 6 11 Ex.8 BzCN + AcOH 100 99 1 1 79 1 3 AcOH: acetic acidAcCN: acetonitrile BzCN: benzonitorile DCE: dichloroethane Com. 1:adamantanol Com. 2: acetyloxyadamantane Com. 3: nitroadmantane Com. 4:adamantanediol Com. 5: nitroadamantanol

Example 9

An eggplant type flask with side arm was dipped in iced water andreduced pressure. Into the flask, not only nitrogen monoxide and oxygenwas introduced from a gasbag (1L). Theflask was filledwithreddish-browngas, and then the reddish-brown gas sedimented to form blueliquid which comprised N₂O₃ as a main component was formed withsedimentation of. The introductions of the nitrogen monoxide and oxygenwere repeated to produce about 1.5 ml of the blue liquid. The blueliquid was frozen with use of liquid nitrogen.

1.8 g (0.024 mole based on N₂O₃ basis) of the frozen blue liquid, 1mmole of adamantane, 0.05 mmole of N-hydroxyphthalimide and 5 ml ofacetic acid were mixed, and then the mixture was reacted for 10 hours at100° C. with stirring. The reaction products were analyzed by gaschromatography, and, as a result, nitroadamantane (yield 81%) was formedwith conversion of 99%.

Example 10

The nitration reaction was effected in the same manner as Example 9except that 1.8 g (0.024 mole based on N₂O₃) of the frozen blue liquid,1 mole of adamantane, 0. 05 mmole of N-hydroxyphthalimide and 5 mlacetic acid were mixed and then the mixture was reacted for 16 hours at25° C. with stirring. As a result, nitroadamantane was formed. Theconversion of adamantane was 83% and the yield of the nitroadamantanewas 72%.

Example 11

Into a flask, 1 mmole of adamantane, 0.1 mmole of N-hydroxyphthalimide,2 ml of nitrogen dioxide (N₂O), 6 ml of benzonitrile (6 ml) and 1.2 mlof acetic acid were added and stirred for 12 hours at 60° C. in anatmosphere of nitrogen monoxide (NO). The reaction products wereanalyzed by gas chromatography, and, as a result, the conversion ofadamantane was 98%, nitroadamantane (yield 68%), adamantanol (yield 6%)and acetyloxyadamantane (yield 4%) were formed.

Example 12

The reaction was effected in the same manner as Example 11 except forstirring in an atmosphere of oxygen instead of the atmosphere ofnitrogen oxide (NO)). Ni-troadamantane (yield 78%), adamantanol (yield1%), acetyloxyadamantane (yield 1%) andadamantanone (yield 3%) wereformed. The conversion of adamantane was 98%.

Example 13

The reaction was effected in the same manner as Example 11 except forstirring in an atmosphere of an inert gas (argon) instead of theatmosphere of nitrogen oxide (NO)). Nitroadamantane (yield 76%),adamantanol (yield 1%), acetyloxyadamantane (yield 6%) andadamantanon(yield 6%) were formed. The conversion of adamantane was 97%.

Example 14

Into a flask, 1 mmole of ethylbenzene, 0.05 mmole ofN-hydroxyphthalimide and 5 ml of acetic acid were added to mix and theflask was equipped with a gas bag (about 1L)of nitrogen monoxide NO. Themixture was reacted for 8 hours at 100° C. with stirring. The reactionproducts were analyzed by gas chromatography, and, as a result, theconversion of ethylbenzene was 85%, and 1-nitroethylbenzene (yield 14%),1-hydroxyethylbenzene (yield 18%) and 1-acetyloxyethylbenzene (yield30%) were formed.

Example 15

Into a flask, 1 mmole of adamantane, 0.1 mmole of N-hydroxyphthalimideand 6 ml of acetic acid were added to mix. The flask was purged bynitrogen monoxide NO (about 1L) and oxygen O² (about 1L), and then themixture was reacted for 20 hours at 110° C. with stirring. The reactionproducts were analyzed by gas chromatography, and, as a result, theconversion of adamantane was 90%, and 1-nitroadamantane (yield 64%) and1,3-dinitroadamantane (yield 12%) were formed.

Example 16

The operation was effected in the same manner as Example 15 except forusing 1-nitroadamantane instead of adamantane.1,3-dinitroadamantane(yield 80%)wasformed. The conversion of1-nitroadamantane was 90%. Incidentally, when the reaction time was 6hours, the conversion of 1-nitroadamantane was 33% and the yield of1,3-dinitroadamantane was 27%.

Pale yellow solid; Mass spectral data [M]⁺: 226; IR(cm⁻¹): 1560, 1360,750.

Example 17

Into a flask, 1 mmole of adamantane, 0.1 mmole of N-hydroxyphthalimide,6 ml of benzonitrile and 1 ml of acetic acid were added to mix and theflask was equipped with a gas bag (about 1L) of nitrogen monoxide NO.The mixture was reacted for 20 hours at 100° C. with stirring. Thereaction products were analyzed by gas chromatography, and, as a result,the conversion of adamantane was 92%, and 1-benzoylaminoadamantane(yield 65%), 1-adamantanol (yield 7%), 1-nitroadamantane (yield 6%),1-acetyloxyadamantane (yield 2%) and 2-adamantanone (yield 2%) wereformed.

Example 18

Into a flask, 2 mmole of toluene, 0.2 mmole of N-hydroxyphthalimide, 6ml of 1,2-dichloroethane and 1.2 ml of acetonitrile were added to mix.The mixture was reacted for 12 hours at 60° C. with stirring in anatmosphere of nitrogen dioxide NO₂. The reaction products were analyzedby gas chromatography, and, as a result, the conversion of toluene was47%, and 2-nitrotoluene (yield 18%), nitromethylbenzene (yield 9%) and4-nitrotoluene (yield 9%) were formed.

Example 19

The operation was effected in the same manner as Example 18 except forconducting the reaction after purged by nitrogen monoxide NO and oxygenO₂ (molar ratio 1:1) to reaction system instead of nitrogen dioxide NO₂.2-nitrotoluene (yield 20%), nitromethylbenzene (yield 7%) and4-nitrotoluene (yield 3%) were formed. The conversion of toluene was52%.

Example 20

The operation was effected in the same manner as Example 19 except forusing ethylbenzene instead of toluene. The conversion of ethylbenzenewas 100%, and 1-nitroethylbenzene (yield 13%), 2-nitro-1-ethylbenzene(yield 21%) and 4-nitro-1-ethylbenzene (yield 18%) were formed.

Example 21

The operation was effected in the same manner as Example 20 except forusing nitrogen dioxide NO₂ and oxygen O₂ (molar ratio 1:1) instead ofnitrogen monoxide NO and oxygen O₂ and reacting for 8 hours. Theconversion of ethylbenzene was 100%, and 1-nitroethylbenzene (yield15%), o-nitroethylbenzene (yield 19%) and m-nitroethylbenzene (yield13%) were formed.

Example 22

The operation was effected in the same manner as Example 20 except forusing nitrogen dioxide NO₂ and nitrogen monoxide NO (molar ratio 1:1)instead of nitrogen monoxide NO and oxygen O₂ and reacting for 8 hours.The conversion of ethylbenzene was 91%, and 1-nitroethylbenzene (yield11%), o-nitroethylbenzene (yield 3%) and acetophenone (yield 14%) wereformed.

Example 23

Into a flask, 1 mmole of adamantane, 0.05 mmole of N-hydroxyphthalimide,15 mmole of nitrogen dioxide (NO₂) and 3 ml of acetonitrile were addedand stirred for 5 hours at 60° C. in an atmosphere of oxygen. Thereaction products were analyzed by gas chromatography, and, as a result,the conversion of adamantane was 97%, and nitroadamantane (yield 65%),dinitroadamantane (yield 1%), adamantanol (yield 1%),acetyloxyadamantane (yield 3%) and adamantanone (yield 2%) were formed.

Example 24

The reaction was effected in the same manner as Example 23 except thatthe amount of N-hydroxyphthalimide was 0.1 mmole and the reaction timewas 3 hours. The conversion of adamantane was 98%, and nitroadamantne(yield 69%), adamantanol (yield 1%), acetyloxyadamantane (yield 2%) andadamantanone (yield 2%) were formed.

Example 25

Into a flask, 1 mmole of adamantane, 0.05 mmole of N-hydroxyphthalimide,15 mmole of nitrogen dioxide (NO₂) and 3 ml of trifluoromethylbenzenewere added and stirred for 5 hours at 60° C. in an atmosphere of oxygen.The reaction products were analyzed by gas chromatography, and, as aresult, the conversion of adamantane was 79%, and nitroadamantane (yield57%), adamantanol (yield 6%) and adamantanone (yield 4%) were formed.

Example 26

The reaction was effected in the same manner as Example 25 except thatthe amount of N-hydroxyphthalimide was 0.1 mmole. The conversion ofadamantane was 96%, and nitroadamantane (yield 66%), adamantanol (yield4%) and adamantanone (yield 5%) were formed.

Example 27

Into a flask, 1 mmole of adamantane, 0.05 mmole of N-hydroxyphthalimide,15 mmole of nitrogen dioxide (NO₂), 1 ml of acetonitrile and 2 ml oftrifluoromethylbenzene were added and stirred for 5 hours at 60° C. inan atmosphere of oxygen. The reaction products were analyzed by gaschromatography, and, as a result, the conversion of adamantane was 90%,and nitroadamantane (yield 73%), adamantanol (yield 2%),acetyloxyadamantane (yield 1%) and adamantanone (yield 3%) were formed.

Example 28

The reaction was effected in the same manner as Example 27 except thatthe amount of N-hydroxyphthalimide was 0.1 mmole. The conversion ofadamantane was 95%, and nitroadamantane (yield 76%), adamantanol (yield1%), acetyloxyadamantane (yield 1%) and adamantanone (yield 3%) wereformed.

Example 29

The reaction was effected in the same manner as Example 28 except thatthe amount of acetonitrile was 0.5 ml and that the amount oftrifluoromethylbenzene was 2.5 ml. The conversion of adamantane was 89%,and nitroadamantane (yield 70%), adamantanol (yield 1%),acetyloxyadamantane (yield 1%) and adamantanone (yield 4%) were formed.

Example 30

Into a flask, 1 mmole of adamantane, 0.05 mmole of N-hydroxyphthalimide,15 mmole of nitrogen dioxide (NO₂) and 3 ml of dichloroethane were addedand stirred for 5 hours at 60° C. in an atmosphere of oxygen. Thereaction products were analyzed by gas chromatography, and, as a result,the conversion of adamantane was 97%, and nitroadamantane (yield 57%),adamantanol (yield 12%) and adamantanone (yield 4%) were formed.

Example 31

Into a flask, 1 mmole of adamantane, 0.1 mmole of N-hydroxyphthalimide,15 mmole of nitrogen dioxide (NO₂) and 3 ml of acetic acid were addedand stirred for 5 hours at 60° C. in an atmosphere of oxygen. Thereaction products were analyzed by gas chromatography, and, as a result,the conversion of adamantane was. 96%, and nitroadamantane (yield 75%),adamantanol (yield 1%), acetyloxyadamantane (yield 5%) and adamantanone(yield 4%) were formed.

Example 32

Into a flask, 1 mmole of adamantane, 0.1 mmole of N-hydroxyphthalimide,0.0005 mmole of acetylacetonatomanganese(II) Mn(AA)₂ and 5 ml of aceticacid were added to mix and the flask was equipped with a gas bag (about1L) of nitrogen monoxide NO. The mixture was reacted for 8 hours at 100°C. with stirring. The reaction products were analyzed by gaschromatography, and, as a result, the conversion of adamantane was 95%,and nitroadamantane (yield 75%) was formed.

Example 33

The reaction was effected in the same manner as Example 32 except forusing acetylacetonatomanganese (III) Mn(AA)₃ instead of Mn(AA)₂. Theconversion of adamantane was 72%, and nitroadamantane (yield 66%) wasformed.

Example 34

The reaction was effected in the same manner as Example 32 except forusing molybdic acid H₂MoO₄ instead of Mn(AA)₂. The conversion ofadamantane was 62%, and nitroadamantane (yield 57%) was formed.

Example 35

The reaction was effected in the same manner as Example 32 except forusing acetylacetonatoiron(III) Fe(AA)₃ instead of Mn(AA)₂. Theconversion of adamantane was 56%, and nitroadamantane (yield 50%) wasformed.

Example 36

The reaction was effected in the same manner as Example 32 except forusing managanese acetate Mn(Oac)₂ instead of Mn(AA)₂. The conversion ofadamantane was 77%, and nitroadamantane (yield 72%) was formed.

Example 37

The reaction was effected in the same manner as Example 32 except forusing 0.0001 mmole of acetylacetonatocobalt(II) Co(AA)₂ instead ofMn(AA)₂. The conversion of adamantane was 82%, and nitroadamantane(yield 75%) was formed.

Example 38

The reaction was effected in the same manner as Example 32 except forusing acetylacetonatonickel(II) Ni(AA)₂ instead of Mn(AA)₂. Theconversion of adamantane was 54%, and nitroadamantane (yield 49%) wasformed.

Example 39

The reaction was effected in the same manner as Example 32 except forusing acetylacetonatochromium(III) Cr(AA)₃ instead of Mn(AA)₂. Theconversion of adamantane was 72%, and nitroadamantane (yield 66%) wasformed.

Example 40

The reaction was effected in the same manner as Example 32 except forusing acetylacetonatocopper(II) Cu(AA)₂ instead of Mn(AA)₂. Theconversion of adamantane was 52%, and nitroadamantane (yield 46%) wereformed.

Example 41

The reaction was effected in the same manner as Example 32 except forusing acetylacetonatocopper(III) Cu(AA)₃ instead of Mn(AA)₂. theconversion of adamantane was 48%, and nitroadamantane (yield 42%) wereformed.

Example 42

Into a flask, 1 mmole of 1-carboxyadamantane, 0.1 mmole ofN-hydroxyphthalimide and 6 ml of acetic acid were added to mix. Themixture was purged by nitrogen monoxide NO (about 1L) and oxygen O₂(about 1L), and then reacted for 20 hours at 110° C. with stirring. Thereaction products were analyzed by gas chromatography, and, as a result,the conversion of 1-carboxyadamantane was 90%, and1-carboxy-3-nitroadamantane (yield 80%) was formed.

Pale yellow solid; Mass spectral data [M]⁺: 225; IR(cm⁻¹): 2990, 1620,1560;

Example 43

The reaction was effected in the same manner as Example 42 except forusing 1-hydroxymethyladamantane instead of 1-carboxyadamantane. Theconversion of 1-hydroxymethyladamantane was 90%, and1-hydroxymethyl-3-nitroadamantane (yield 70%) was formed.

Pale yellow solid; Mass spectral data [M]⁺: 211; IR(cm⁻¹): 3350, 1550,1370;

Example 44

To acetic acid, the mixture of 10 mmole of adamantane, 1 mmole of N-hydroxyphthalimide (NHPI) and 0.005 mmole of acetylaceto natocobalt(II)Co(AA)₂ was charged and the container was equipped with a gas bagcharged with mixed gas (mixed gas comprised 2L of carbon monoxide and0.5L of oxygen; pressure: 5 kg/cm²). The mixture was stirred f or 6hours at 60° C. The products in the reaction mixture were analyzed bygas chromatography, and, as a result, the conversion of adamantane was76%, and 1-carbpxyadamantane (yield 70%) was formed.

Example 45

The reaction was effected in the same manner as Example 44 except forusing acetylacetonatomanganese(II) Mn(AA)₂ instead of Co(AA)₂. Theconversion of adamantane was 68%, and 1-carboxyadamantane (yield 62%)were formed.

Example 46

The reaction was effected in the same manner as Example 44 except forusing acetonitrile instead of acetic acid. The conversion of adamantanewas 73%, and 1-carboxyadamantane (yield 69%) were formed.

Example 47

The reaction was effected in the same manner as Example 44 except forusing dichloroethane instead of acetic acid. The conversion ofadamantane was 81%, and 1-carboxyadamantane (yield 75%) were formed.

Example 48

The reaction was effected in the same manner as Example 44 except thatthe reaction temperature was 80° C. The conversion of adamantane was87%, and 1-carboxyadamantane (yield 81%) was formed.

Example 49

The reaction was effected in the same manner as Example 44 except forusing 1-methyladamantane instead of adamantane. The conversion of 1-methyladamantane was 71%, and 1-carboxy-3-methyladamantane (yield 66%)was formed.

Example 50

The reaction was effected in the same manner as Example 44 except forusing toluene instead of adamantane. The conversion of toluene was 67%,and phenyl acetate (yield 61%) were formed.

Example 51

The reaction was effected in the same manner as Example 44 except forusing ethylbenzene instead of adamantane and that the pressure of themixed gas was 10 kg/cm². The conversion of ethylbenzene was 71%, and1-phenylpropionic acid (yield 56%) was formed.

Example 52

The reaction was effected in the same manner as Example 44 except forusing fluorene instead of adamantane and that the pressure of the mixedgas was 10 kg/cm². The conversion of fluorene was 73%, and9-carboxyfluorene (yield 69%) were formed.

Example 53

To the solvent mixture of 3 ml of acetic acid and 3 ml of1,2-dichloroethane, a mixture of 10 mmole oftetrahydrodicyclopentadiene, 3 mmole of N-hydroxyphthalimide(NHPI) and0.05 mmole of acetylaceto-natocobalt(II) Co(AA)₂ was charged. Thereaction mixture was stirred for 15 hours at 85° C. in an atmosphere ofmixed gas of carbon monoxide and air (partial pressure of carbonmonoxide: 45 kg/cm², partial pressure of air: 1 kg/cm²). The products inthe reaction mixture were analyzed by gas chromatography, and, as aresult, the conversion of tetrahydrodicyclopentadiene was 68%, and1-carboxytetrahydrodicyclopentadiene (yield 38%) was formed.

Example 54

The reaction was effected in the same manner as Example 53 except forusing acetylacetonatomanganese(II) Mn(AA)₂ instead of Co(AA)₂. Theconversion of tetrahydrodicyclopentadiene was 66%, and1-carboxytetrahydrodicyclopentadiene (yield 38%) were formed.

Example 55

The reaction was effected in the same manner as Example 44 except forusing acetylacetonatomanganese(III) Mn(AA)₃ instead of Co(AA)₂. Theconversion of adamantane was 66%, and 1-carboxyadamantane (yield 62%)was formed.

Example 56

The reaction was effected in the same manner as Example 44 except forusing molybdic acid H₂MoO₄ instead of Co(AA)₂. The conversion ofadamantane was 58%, and 1-carboxyadamantane (yield 52%) was formed.

Example 57

The reaction was effected in the same manner as Example 44 except forusing acetylacetonatoiron(III) Fe(AA)₃ instead of Co(AA)₂. Theconversion of adamantane was 52%, and 1-carboxyadamantane (yield 50%)was formed.

Example 58

The reaction was effected in the same manner as Example 44 except forusing manganese acetate Mn(OAc)₂ instead of Co(AA)₂. The conversion ofadamantane was 71%, and 1-carboxyadamantane (yield 66%) was formed.

Example 59

The reaction was effected in the same manner as Example 44 except forusing 0.005 mmole of acetylacetonatomanganese(II) Mn(AA)₂ and 0.001mmole of Co(AA)₂ instead of Co(AA)₂. The conversion of adamantane was74%, and 1-carboxyadamantane (yield 71%) was formed.

Example 60

The reaction was effected in the same manner as Example 44 except forusing acetylacetonatonickel(III) Ni(AA)₂ instead of Co(AA)₂. Theconversion of adamantane was 51%, and 1-carboxyadamantane (yield 47%)was formed.

Example 61

The reaction was effected in the same manner as Example 44 except forusing acetylacetonatochromium(III) Cr(AA)₃ instead of Co(AA)₂. Theconversion of adamantane was 62%, and 1-carboxyadamantane (yield 60%)was formed.

Example 62

The reaction was effected in the same manner as Example 44 except forusing acetylacetonatocopper(II) Cu(AA)₂ instead of Co(AA)₂. Theconversion of adamantane was 47%, and 1-carboxyadamantane (yield 41%)was formed.

Example 63

The reaction was effected in the same manner as Example 44 except forusing acetylacetonatocopper(III) Cu(AA)₃ instead of Co(AA)₂. Theconversion of adamantane was 48%, and 1-carboxyadamantane (yield 43%)was formed.

Example 64

The reaction was effected in the same manner as Example 44 except forusing 1-carboxyadamantane instead of adamantane. The conversion of1-carboxyadamantane was 80%, and 1,3-dicarboxyadamantane (yield 70%) wasformed.

White solid; Mass spectral data [M]⁺: 224; IR(cm⁻¹): 3010, 1630, 1140.

Comparative Example 1

The stirring was carried out in the same manner as Example 44 withoutuse of NHPI. No carboxyadamantane was detected.

Comparative Example 2

The stirring was carried out in the same manner as Example 44 withoutuse of oxygen. No carboxyadamantane was detected.

Example 65

To an autoclave, 10 mmole of 1,3-dinitroadamantane obtained by themethod of Example 16, 5% Pd-C (10 mole % of Pd relative to a substrate),1 ml of dilute hydrochloric acid and 10 ml of methanol were charged. Themixture was stirred for 2 hours at 80° C. in an atmosphere of hydrogenat 30 atm. As a result, the conversion of 1,3-dinitroadamantane was 99%,and 1,3-diaminoadamantane (yield 95%) was formed.

Pale yellow solid; Mass spectral data [M]⁺: 166; IR(cm⁻¹): 3310, 1520,870.

Example 66

The reaction was effected in the same manner as Example 65 except forusing Raney nickel (5 mole % of Ni relative to a substrate) instead of5% Pd-C and that reacting for 4 hours. The conversion of1,3-dinitroadamantane was 99%, and 1-amino-3-nitroadamantane (yield 80%)was formed.

Pale yellow solid; Mass spectral data [M]⁺: 166; IR(cm⁻¹): 3310, 1520,870.

Example 67

In an atmosphere of nitrogen, 11 mmole of acetyl chloride and 12 mmoleof triethylamine were dissolved in 2 ml of tetrahydrofurane (THF). Tothe resultant solution, 10 mmole of 1-amino-3-nitroadamantane obtainedby the method of Example 66 and 10 ml of N,N-dimethylformamide (DMF)were added. The mixture was stirred for 3 hours at 40° C. As a result,the conversion of 1-amino-3-nitroadamantane was 99%, and1-acetylamino-3-nitroadamantane (yield 95%) was formed.

Pale yellow liquid; Mass spectral data [M]⁺: 238; IR(cm⁻¹): 1680, 1550,680.

Example 68

In an atmosphere of nitrogen, 10 mmole of 1-carboxy-3-nitroadamantaneobtained by the method of Example 42 was dissolved in 10ml of DMF. Tothe mixture, 15 mmole of acetyl chloride was added dropwise over 30minutes. The mixture was heated to begin to reflux around the conclusionof the addition. After refluxing for 2 hours, the mixture was cooled, 20mmole of triethylamine was added, and then 11 mmole of methanol wasadded dropwise over 30 minutes while retaining the temperature of themixture at 10° C. or less followed by stirring for more 2 hours. As aresult, the conversion of 1-carboxy-3-nitroadamantane was 99%, and1-methoxycarbonyl-3-nitroadamantane (yield 95%) was formed.

Pale yellow solid; Mass spectral data [M]⁺: 239; IR(cm⁻¹): 1730, 1560,1120.

Example 69

In an atmosphere of nitrogen, 10 mmole of 1-carboxy-3-nitroadamantaneobtained by the method of Example 43 was dissolved in 10 ml of DMF. Tothe mixture, 15 mmole of acetyl chloride was added dropwise over 30minutes. The mixture was heated to begin to reflux around the conclusionof the addition. After refluxing for 2 hours, the mixture was cooled,and25 mmole of dimethylamine was added dropwise over 30 minutes whileretaining the temperature of the mixture at 10° C. or less followed bystirring for more 2 hours. As a result, the conversion of1-carboxy-3-nitroadamantane was 99%, and1-(N,N-dimethylcarbamoyl)-3-nitroadamantane (yield 95%) was formed.

Pale yellow solid; Mass spectral data [M]⁺: 252; IR(cm⁻¹): 1660, 1560,690.

Example 70

The operation was effected in the same manner as Example 57 except forusing 1-carboxy-3-nitroadamantane obtained by the method of Example 42instead of 1,3-dinitroadmantane. The conversion of1-carboxy-3-nitroadamantane was 80%, and 1-amino-3-carboxyadamantane(yield 70%) was formed.

Pale yellow solid; Mass spectral data [M]⁺: 195; IR(cm⁻¹): 3370, 3000,1670, 1620.

Example 71

The operation was effected in the same manner as Example 67 except forusing 1-amino-3-carboxyadamantane obtained by the method of Example 70instead of 1-amino-3-nitroadmantane. The conversion of1-amino-3-carboxyadamantane was 99%, and1-acetylamino-3-carboxyadamantane (yield 95%) was formed.

Pale yellow liquid; Mass spectral data [M]⁺: 234; IR(cm⁻¹): 3360, 1670,1640.

Example 72

The operation was effected in the same manner as Example 68 except forusing 1,3-dicarboxyadamantane obtained by the method of Example 64instead of 1-carboxy-3-nitroadmantane. The conversion of1,3-dicarboxyadamantane was 90%, and1-carboxy-3-methoxycarbonyladamantane (yield 80%) was formed.

White solid; Mass spectral data [M]⁺: 238; IR(cm⁻¹): 3030, 1670, 1630.

Example 73

In an atmosphere of nitrogen, 15 mmole of lithium aluminum hydride wassuspended in 15 ml of THF. To the mixture, 10 mmole of1,3-dicarboxyadamantane obtained by the method of example 64 was addedslowly while retaining the temperature of the mixture at 10° C. or lesswith use of an ice bath. After warming to the room temperature, themixture was refluxed for 16 hours. As a result, The conversion of1,3-dicarboxyadamantane was 90%, and 1-carboxy-3-hydroxymethyladamantane(yield 80%) was formed.

White solid; Mass spectral data [M]⁺: 210; IR(cm⁻¹): 3350, 3000, 1650.

Example 74

The operation was effected in the same manner as Example 69 except forusing 1,3-dicarboxyadamantane obtained by the method of Example 64instead of 1-carboxy-3-nitroadmantane. The conversion of1,3-dicarboxyadamantane was 90%, and1-carboxy-3-(N,N-dimethylcarbamoyl)adamantane (yield 80%) was formed.

Pale yellow solid; Mass spectral data [M]⁺: 251; IR(cm⁻¹): 3010, 1670,1630.

Example 75

The operation was effected in the same manner as Example 67 except forusing 1, 3-diaminoadamantane obtained by the method of Example 65instead of 1-amino-3-nitroadmantane. The conversion of1,3-diaminoadamantane was 90%, and 1-acetylamino-3-aminoadamantane(yield 80%) was formed.

Pale yellow liquid; Mass spectral data [M]⁺: 208; IR(cm⁻¹): 3350, 1660,760.

Example 76

The operation was effected in the same manner as Example 68 except forusing 1-amino-3-carboxyadamantane obtained by the method of Example 70instead of 1-carboxy-3-nitroadmantane. The conversion of1-amino-3-carboxyadamantane was 99%, and1-amino-3-methoxycarbonyladamantane (yield 95%) was formed.

Pale yellow solid; Mass spectral data [M]⁺: 209; IR(cm⁻¹): 3330, 1630,770.

Example 77

The operation was effected in the same manner as Example 66 except forusing 1-hydroxymethyl-3-nitroadamantane obtained by the method ofExample 43 instead of 1,3-dinitroadmantane. The conversion of1-hydroxymethyl-3-nitroadamantane was 99%, and1-amino-3-hydroxymethyladamantane (yield 95%) was formed.

Pale yellow solid; Mass spectral data [M]⁺: 181; IR(cm⁻¹): 3300, 1160,760.

Example 78

The operation was effected in the same manner as Example 66 except forusing 1-(N,N-dimethylcarbamoyl)-3-nitroadamantane obtained by the methodof Example 69 instead of 1,3-dinitroadmantane. The conversion of1-(N,N-dimethylcarbamoyl)-3-nitroadamantane was 90%, and1-amino-3-(N,N-dimethylcarbamoyl) adamantane (yield 80%) was formed.

Pale yellow solid; Mass spectral data [M]⁺: 222; IR(cm⁻¹): 3310, 1670,1140.

Example 79

The operation was effected in the same manner as Example 68 except forusing 1-acetylamino-3-carboxyadamantane obtained by the method ofExample 71 instead of 1-carboxy-3-nitroadmantane.1-acetylamino-3-methoxycarbonyladamantane (yield 80%) was formed. Theconversion of 1-acetylamino-3-carboxyadamantane was 90%.

Pale yellow liquid; Mass spectral data [M]⁺: 251; IR(cm⁻¹): 3300, 1660,1620.

Example 80

The operation was effected in the same manner as Example 67 except forusing 1-amino-3-hydroxymethyladamantane obtained by the method ofExample 77 instead of 1-amino-3-nitroadmantane. The conversion of1-amino-3-hydroxymethyladamantane was 90%, and1-acetylamino-3-hydroxymethyladamantane (yield 80%) was formed.

Pale yellow liquid; Mass spectral data [M]⁺: 223; IR(cm⁻¹): 3310, 1650,1160.

Example 81

The opeartion was effected in the same manner as Example 67 except forusing 1-amino-3-(N,N-dimethylcarbamoyl)adamantane obtained by the methodof Example 78 instead of l-amino-3-nitroadmantane. The conversion of1-amino-3-(N,N-dimethylcarbamoyl)adamantane was 90%, and1-acetylamino-3-(N,N-dimethylcarbamoyl)adamantane (yield 80%) wasformed.

Pale yellow solid; Mass spectral data [M]⁺: 264; IR(cm⁻¹): 3300, 1670,1650, 740.

Example 82

The operation was effected in the same manner as Example 68 except forusing 1-hydroxymethyl-3-carboxyadamantane obtained by the method ofExample 73 instead of 1-carboxy-3-nitroadmantane. The conversion of1-hydroxymethyl-3-carboxyadamantane was 90%, and1-hydroxymethyl-3-methoxycarbonyladamantane (yield 80%) was formed.

White solid; Mass spectral data [M]⁺: 224; IR(cm⁻¹): 3310, 1620, 1430.

Example 83

In an atmosphere of nitrogen, 22 mmole of acetyl chloride and 24 mmoleof triethylamine were dissolved in 2 ml of tetrahydrofurane (THF). Tothe resultant solution, 10 ml of solution containing 10 mmole of1,3-diaminoadamantane obtained by the method of Example 65 inN,N-dimethylformamide (DMF) was added and then stirred for 3 hours at40° C. As a result, the conversion of 1,3-diaminoadamantane was 99%, and1,3-bis(acetylamino)adamantane (yield 95%) was formed.

Pale yellow liquid; Mass spectral data [M]⁺: 250; IR(cm⁻¹): 3330, 1660,1240.

Example 84

In an atmosphere of nitrogen, 10 mmole of 1,3-dicarboxyadamantaneobtained by the method of Example 64 was dissolved in 10 ml of DMF. Tothe mixture, 30 mmole of thionyl chloride was added dropwise over 30minutes and the mixture was heated to begin to reflux around theconclusion of addition. After refluxing for 2 hours, the mixture wascooled. To the mixture, 40 mmole of triethylamine was added followed by22 mmole of methanol over 30 minutes while retaining the temperature ofthe mixture at 10° C. or less, and then stirred for more 2 hours. As aresult, the conversion of 1, 3-dicarboxyadamantane was 99%, and1,3-bis(methoxycarbonyl)adamantane (yield 95%) was formed.

White solid; Mass spectral data [M]⁺: 252; IR(cm⁻¹): 1620, 1240, 1030.

Example 85

In an atmosphere of nitrogen, 30 mmole of lithium aluminum hydride wassuspended in 15 ml of THF. To the mixture, 10 mmole of1,3-dicarboxyadamantane obtained by the method of Example 64 was addedslowly while retaining the temperature of the mixture at 10° C. or lesswith use of a ice bath. After heating to the room temperature, themixture was refluxed for 16 hours. As a result, the conversion of1,3-dicarboxyadamantane was 99%, and 1,3-bis(hydroxymethyl)adamantane(yield 95%) was formed.

White solid; Mass spectral data [M]⁺: 196; IR(cm⁻¹): 3310, 1490, 720.

Example 86

In an atmosphere of nitrogen, 10 mmole of 1,3-dicarboxyadamantaneobtained by the method of Example 64 was dissolved in 10 ml of DMF. Tothe mixture, 30 mmole of thionyl chloride was added dropwise over 30minutes and the mixture was heated to begin to reflux around theconclusion of addition. After refluxing for 2 hours, the mixture wascooled. To the mixture, 50 mmole of dimethylamine was added dropwiseover 30 minutes while retaining the temperature of the mixture at 10° C.or less, and then stirred for more 2 hours. As a result, the conversionof 1,3-dicarboxyadamantane was 99%, and1,3-bis(N,N-dimethylcarbamoyl)adamantane (yield 95%) was formed.

Pale yellow solid; Mass spectral data [M]⁺: 278; IR(cm⁻¹): 1670, 1420,1170.

Example 87

1 mmole of 1,3-bis(methozxycarbonyl)adamantane obtained by the method ofExample 84 was dissolved in 30 ml of THF. To the mixture, 0.5 mmole ofdimethylamine and 0.1 mmole of aluminum chloride anhydride AlCl₃ wasadded and reacted for 6 hours at 80° C. As a result, The conversion of1,3-bis(methoxycarbonyl)adamantane was 90%, and1-methoxycarbonyl-3-(N,N-dimethylcarbamoyl)adamantane (yield 80%) wasformed.

Pale yellow solid; Mass spectral data [M]⁺: 265; IR(cm⁻¹): 1670, 1630,1170.

Example 88

In an atmosphere of nitrogen, 10 mmole of1-carboxy-3-hydroxymethyladamantane obtained by the method of Example 73was dissolved in 10 ml of DMF. To the mixture, 15 mmole ofN,N′-carbodiimidazol in the form of powder was added in one portion.After stirring for 1 hour at the room temperature, 15 mmole ofdimethylamine and 15 mmole of diazabicycloundecene were added. Themixture was heated to 100° C. and stirred f or 8 hours. As a result, theconversion of 1-carboxy-3-hydroxymethyladamantane was 99%, and1-hydroxymethyl-3-(N,N-dimethylcarbamoyl)adamantane (yield 95%) wasformed.

Pale yellow liquid; Mass spectral data [M]⁺: 237; IR(cm⁻¹): 3310, 1660,1220.

Example 89

10 mmole of 1-amino-3-nitroadamantane obtained by the method of Example66 was dissolved in toluene (100 ml). To the resultant solution, 12mmole of phosgene was added at the room temperature and stirred for 6hours. As a result, The conversion of 1-amino-3-nitroadamantane was 99%,and 1-isocyanato-3-nitroadamantane (yield 90%) was formed.

Pale yellow liquid; Mass spectral data [M]⁺: 222; IR(cm⁻¹): 2200, 1560,1330, 750.

Example 90

The operation was effected in the same manner as Example 89 except forusing 1-aminoadamantane instead of 1-amino-3-nitroadmantane. Theconversion of 1-aminoadamantane was 99%, and 1-isocyanatoadamantane(yield 90%) was formed.

Pale yellow liquid; Mass spectral data [M]⁺: 177; IR(cm⁻¹): 3300, 2180,1270.

Example 91

The operation was effected in the same manner as Example 80 except forusing 1,3-diaminoadamantane obtained by the method of Example 65 insteadof 1-amino-3-nitroadmantane. The conversion of 1,3-diaminoadamantane was90%, and 1-isocyanatoademantane (yield 80t) was formed.

Pale yellow liquid; Mass spectral data [M]⁺: 192; IR(cm⁻¹): 3310, 2270,1520, 870.

Example 92

The operation was effected in the same manner as Example 89 except forusing 1-amino-3-(N,N-dimethylcarbamoyl)adamantane obtained by the methodof Example 78 instead of 1-amino-3-nitroadmantane. The conversion of1-amino-3-(N,N-dimethylcarbamoyl)adamantane was 95%, and1-isocyanato-3-(N,N-dimethylcarbamoyl)adamantane (yield 85%) was formed.

Pale yellow liquid; Mass spectral data [M]⁺: 248; IR(cm⁻¹): 2200, 1640,1310, 750.

Example 93

The operation was effected in the same manner as Example 89 except forusing 1-amino-3-methoxycarbonyladamantane obtained by the method ofExample 78 instead of 1-amino-3-nitroadmantane. The conversion of1-amino-3-methoxycarbonyladamantane was 95%, and1-isocyanato-3-methoxycarbonyladamantane (yield 85%) was formed.

Pale yellow liquid; Mass spectral data [M]⁺: 235; IR(cm⁻¹): 2220, 1640,1330, 770.

Example 94

To the mixture of 10 mmole of adamantane, 1 mmole of NHPI, 0.005 mmoleof Co(AA)₂ and 25 ml of acetic acid, nitrogen monoxide (NO), carbonmonoxide (CO) and oxygen (O₂) were introduced in the ratio of NO:CO:O₂(molar ratio)=10:15:1 at the pressure of 26 kg/cm² and then stirred for6 hours at 100° C. The reaction products were analyzed by gaschromatography and gas-mass spectrum apparatus, and as a result,1,3,5-trinitroadamantane (yield 5%), 1-carboxy-3,5-dinitroadamantane(yield 5%), 1,3-dicarboxy-5-nitroadamantane (yield 1%) and1,3,5-tricarboxyadamantane (yield 1%) were formed.

What is claimed is:
 1. A process which comprises contacting a substratewith at least one reactant selected from (i) a nitrogen oxide and (ii) amixture of carbon monoxide and oxygen at least in the presence of acatalyst to introduce at least one functional group selected from anitro group and a carboxyl group to the substrate, wherein the catalystcomprises an imide compound shown by the following formula (1):

wherein R¹ and R² may be same or different from each other, andrepresent a hydrogen atom, a halogen atom, an alkyl group, an arylgroup, a cycloalkyl group, a hydroxyl group, an alkoxy group, a carboxylgroup, an alkoxycarbonyl group, and an acyl group, and R¹ and R² maybond together to form a double bond, or an aromatic or non-aromaticring; Y represents an oxygen atom or a hydroxyl group; and n denotes aninteger of 1 to
 3. 2. A process according to claim 1, said substrate isa member selected from (a) a compound having a methyl group or amethylene group at an adjacent site of an unsaturated bond, (b) a homo-or hetero cyclic compound having a methylene group, (c) a compoundhaving a methine carbon atom, (d) a compound having a methyl group or amethylene group at an adjacent site of an aromatic ring and (e) acompound having a methylene group at an adjacent site of a carbonylgroup.
 3. A process according to claim 1, said substrate is a compoundhaving a methine carbon atom or a compound having a methyl or methylenegroup at a benzyl site of the compound.
 4. A process according to claim1, wherein said nitrogen oxide is shown by the formula: N_(x)O_(y)wherein x denotes an integer of 1 or 2 and y denotes an integer of 1 to6.
 5. A process according to claim 1, wherein said nitrogen oxidecomprises at least one nitrogen compound selected from N₂O₃ and NO₂ as amain component.
 6. A process according to claim 1, wherein not less than1 mole of carbon monoxide and not less than 0.5 mole of oxygen relativeto 1 mole of said substrate are employed.
 7. A process according toclaim 1, a ratio of carbon monoxide to oxygen is carbonmonoxide/oxygen=about 1/99 to 99.99/0.01 (mole ratio).
 8. A processaccording to claim 1 wherein the catalyst comprises said imide compoundshown by the formula (1) and a co-catalyst.
 9. A process for producing acompound having at least one functional group selected from a nitrogroup and a carboxyl group, which comprises, at least in the presence ofa catalyst, contacting a substrate with at least one reactant selectedfrom (i) a nitrogen oxide and (ii) a mixture of carbon monoxide andoxygen, wherein the catalyst comprises an imide compound shown by thefollowing formula (1):

wherein R¹ and R² may be the same or different from each other, andrepresent a hydrogen atom, a halogen atom, an alkyl group, an arylgroup, a cycloalkyl group, a hydroxyl group, an alkoxy group, a carboxylgroup, an alkoxycarbonyl group, and an acyl group, and R¹ and R² maybond together to form a double bond, or an aromatic or non-aromaticring; Y represents an oxygen atom or a hydroxyl group; and n denotes aninteger of 1 to
 3. 10. A process according to claim 9 wherein thecatalyst comprises said imide compound shown by the formula (1) and aco-catalyst.
 11. An adamantane derivative shown by the following formula(2):

wherein X¹ represents a nitro group, an amino group or N-substitutedamino group which may be protected by a protective group, a carboxylgroup which may be protected by a protective group, or a hydroxymethylgroup which may be protected by a protective group; and X³ and X⁴ may bethe same or different from each other, and represents a hydrogen atom,an alkyl group, a nitro group, an amino group or N-substituted aminogroup which may be protected by a protective group, a carboxyl groupwhich may be protected by a protective group, a hydroxymethyl groupwhich may be protected by a protective group or an isocyanato group; (i)when X¹ is a nitro group, X² represents N-amino group which may beprotected by a protective group, a hydroxymethyl group which may beprotected by a protective group, or an isocyanato group; (ii) when X¹ isan amino group or N-substituted amino group which may be protected by aprotective group, X² represents an isocyanato group; (iii) when X¹ is acarboxyl group which may be protected by a protective group, X²represents a hydroxymethyl group which may be protected by a protectivegroup, or an isocyanato group; and (iv) when X¹ is a hydroxymethyl groupwhich may be protected by a protective group, X² represents anisocyanato group; or a salt thereof.
 12. An adamantane derivative shownby the following formula (3):

wherein X⁵ represents a carbamoyl group which may have a substituent, anitro group, a substituted hydroxycarbonylamino group, or a saturatedaliphatic acylamino group or aromatic acylamino group; X⁷ and X8 are thesame or different from each other, and represent a hydrogen atom, analkyl group, a nitro group, an amino or N-substituted amino group whichmay be protected by a protective group, a carboxyl group which may beprotected by a protective group, a hydroxymethyl group which may beprotected by a protective group, or an isocyanato group; (i) when X⁵ isa carbamoyl group which may have a substituent, X⁶ represents a carboxylgroup, a substituted hydroxycarbonyl group, or a nitro group; (ii) whenX⁵ is a nitro group, X⁶ represents a substituted hydroxycarbonyl group;(iii) when X⁵ is a substituted hydroxycarbonylamino group, X⁶ representsa substituted hydroxycarbonyl group, a hydroxymethyl group which may beprotected by a protective group, or an amino group which may beprotected by a protective group; and (iv) when X⁵ is a saturatedaliphatic acylamino group or aromatic acylamino group, X⁶ represents anamino group which may be substituted by an alkyl group; or a saltthereof.
 13. A process for producing a diaminoadamantane derivativeshown by the following formula (2j):

wherein X^(1j) and X^(2j) represent an amino group or N-substitutedamino group which may be protected by a protective group; and X³ and X⁴are the same or different from each other, and represent a hydrogenatom, an alkyl group, a nitro group, an amino group or N-substitutedamino group which may be protected by a protective group, a carboxylgroup which may be protected by a protective group, a hydroxymethylgroup which may be protected by a protective group, or an isocyanatogroup; or a salt thereof, which comprises the steps of contacting acompound shown by the following formula (2h):

wherein X^(2h) represents a hydrogen atom or a nitro group; X³ and X⁴are have the same meanings as defined above; with a nitrogen oxide, inthe presence of an imide compound shown by the following formula (1):

wherein R¹ and R² are the same or different from each other andrepresents a hydrogen atom, a halogen atom, an alkyl group, an arylgroup, a cycloalkyl group, a hydroxyl group, an alkoxy group, a carboxylgroup, an alkoxycarbonyl group, and an acyl group; R¹ and R² may bondtogether to form a double bond, or an aromatic or nonaromatic ring; Yrepresents an oxygen atom or a hydroxyl group; and n denotes an integerof 1 to 3, to produce a dinitroadamantane derivative shown by thefollowing formula (2i):

wherein X^(1i) and X^(2i) each represents a nitro group; and X³ and X⁴have the same meanings as defined above; and reducing saiddinitroadamantane derivative shown by the formula (2i) to produce acorresponding diamino compound.